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Record 1
from database: MEDLINE
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- Title
- Plasma cathepsin activity and
reticuloendothelial phagocytic
function during hemorrhagic shock.
- Author
- Loegering DJ; Carr FK
- Address
-
- Source
- Circ Shock, 1978, 5:1, 61-71
- Abstract
- The present study evaluated two
forms of hemorrhagic shock in terms of
changes in plasma lysosomal enzyme
activity, reticuloendothelial system
(RES) phagocytic function, and plasma
opsonic activity. Hemorrhagic shock
was induced in rats by withdrawal of a
fixed volume of blood equivalent to 3%
body weight or by maintaining the
arterial blood pressure at 40--45 mm
Hg. Plasma cathepsin activity did not
increase until after one hour of
hypotension, and was increased
2.7-fold two hours after a 3% body
weight hemorrhage and 11-fold after
two hours at a blood pressure of
40--45 mm Hg. Phagocytic index and
plasma opsonic activity were decreased
in animals reinfused at 0, 30, or 120
minutes following a 3% body weight
hemorrhage and in animals reinfused 0,
30, and 90 minutes following
hemorrhage to a blood pressure of 40
mm Hg. There was a strong temporal
relationship between the changes in
phagocytic index and plasma opsonic
activity; however, the decrease in RES
function occurred earlier than the
increase in plasma lysosomal enzyme
activity. These results suggest that
the depression of RES function during
shock may be mediated, in part, by a
deficit in circulating opsonic
activity and that RES depression
occurs prior to shock-induced cellular
injury during hemorrhagic shock.
- Language of Publication
- English
- Unique Identifier
- 78167657
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- MeSH Heading (Major)
- Cathepsins|*BL; Phagocytosis|*;
Reticuloendothelial System|EN/*PP;
Shock, Hemorrhagic|EN/*PP
- MeSH Heading
- Animal; Blood Pressure; Lysosomes|EN;
Male; Opsonins|AN; Phagocytes|EN;
Rats; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0092-6213
- Country of Publication
- UNITED STATES
Record 2
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- Title
- Proteolysis of factor V by cathepsin
G and elastase indicates that cleavage
at Arg1545 optimizes cofactor function
by facilitating factor Xa binding.
- Author
- Camire RM; Kalafatis M; Tracy PB
- Address
- Department of Biochemistry,
University of Vermont, College of
Medicine, Burlington, Vermont 05405,
USA.
- Source
- Biochemistry, 1998 Aug, 37:34,
11896-906
- Abstract
- The single-chain procofactor factor
V is cleaved by thrombin (FVaIIa) at
Arg709, Arg1018, and Arg1545 and by a
variety of other proteases to generate
a cofactor species with various levels
of cofactor function. Having
demonstrated previously that monocyte-bound
forms of cathepsin G and elastase
cleave and activate factor V, studies
were initiated here using purified
proteins to probe factor V
structure/function. Electrophoretic,
Western blotting, and amino-terminal
sequence analyses revealed that
cathepsin G cleaves factor V at
several sites (Phe1031, Leu1447,
Tyr1518, and potentially Tyr696),
ultimately generating an
amino-terminal 103 kDa heavy chain and
a carboxy-terminal 80 kDa light chain
(FVaCG). Elastase also cleaves factor
V at several sites (Ile708, Ile819,
Ile1484, and potentially Thr678),
generating a cofactor species, FVaHNE,
with an amino-terminal 102 kDa heavy
chain and a carboxy-terminal 90 kDa
light chain. Incubation of FVaIIa with
either cathepsin G or elastase
resulted in cleavage within the heavy
chain, releasing peptides of
approximately 2000 and approximately
3000 Da, respectively, generating
FVaIIa/CG and FVaIIa/HNE. The
functional activity of each cofactor
species was assessed either by
clotting assay or by employing a
purified prothrombinase assay using
saturating amounts of factor Xa.
Significant differences in cofactor
function were observed between the two
assay systems. Whereas FVaIIa, FVaCG,
FVaIIa/CG, FVaHNE, and FVaIIa/HNE all
had similar cofactor activities in the
purified prothrombinase assay, FVaCG
and FVaHNE had no cofactor activity in
the clotting-based assay, and FVaIIa/CG
and FVaIIa/HNE had approximately
30-35% clotting activity relative to
FVaIIa. These disparate results led us
to examine the binding interactions of
these cofactors with the various
prothrombinase components. Kinetic
analyses indicated that FVaIIa (Kd(app)
= 0.096 nM), FVaIIa/CG (Kd(app) =
0.244 nM), and FVaIIa/HNE (Kd(app) =
0.137 nM) bound to membrane-bound
factor Xa much more effectively than
FVaCG (Kd(app) = 1.46 nM) and FVaHNE (Kd(app)
= 0.818 nM). In contrast, studies of
the activated protein C (APC)-catalyzed
inactivation of each of the factor V(a)
species indicated that they were all
equivalent substrates for APC with no
differences observed in the rate of
inactivation or the cleavage
mechanism, suggesting that APC
interacts with the light chain at a
site distinct from factor Xa. The Km
values for prothrombin, as well as the
kcat values for each of the FV(a)
species, were all similar
(approximately 0.25 microM and
approximately 1900 min-1). In
addition, kinetic analyses indicated
that whereas FVaCG and FVaHNE
exhibited a slightly reduced ability
to interact with phospholipid vesicles
(approximately 2-3-fold), the
remaining FV(a) species assembled
equally well on this surface.
Collectively, these data indicate that
FVaCG and FVaHNE have a diminished
capacity to support factor Xa binding;
however, cleavage at Arg1545 and
removal of the extended B-domain in
these cofactors restore near-total
factor Xa binding. Thus, cleavage at
Arg1545 optimizes cofactor function
within prothrombinase by facilitating
factor Xa binding to membrane-bound
FVa.
- Language of Publication
- English
- Unique Identifier
- 98384156
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- MeSH Heading (Major)
- Arginine|*ME; Cathepsins|*ME/PH;
Factor V|CH/*ME; Factor Xa|*ME;
Pancreatic Elastase|*ME/PH
- MeSH Heading
- Binding Sites; Blood Coagulation
Tests|MT; Catalysis; Enzyme
Activation; Factor Va|ME; Human;
Hydrolysis; Kinetics; Membranes,
Artificial; Phosphatidylcholines|ME;
Phosphatidylserines|ME; Protein
Binding; Protein C|ME; Prothrombin|ME;
Support, Non-U.S. Gov't; Support, U.S.
Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-2960
- Country of Publication
- UNITED STATES
Record 3
from database: MEDLINE
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- Title
- Human leucocyte elastase and
cathepsin G: structural and functional
characteristics.
- Author
- Travis J; Giles PJ; Porcelli L;
Reilly CF; Baugh R; Powers J
- Address
-
- Source
- Ciba Found Symp, 1979, :75, 51-68
- Abstract
- Two of the major enzymes present in
an released from neutrophil
granulocytes are the endoproteinases
elastase and cathepsin G. While the
former is believed to be one of the
major causative agents responsible for
tissue destruction in emphysema and
rheumatoid arthritis, little is known
about the function of cathepsin G. We
have recently developed simple
procedures for isolating the
isoenzymes of each type of proteinase
as well as for their specific
controlling plasma inhibitors. We have
also prepared synthetic substrates and
inhibitor analogues. Some sequence
studies have been initiated and the
results indicate homology of these
enzymes not only with each other and
with the pancreatic proteinases but
also between cathepsin G and
proteolytic enzymes present in muscle
and mast cell tissue. Significantly,
both types of enzyme can degrade the
structural protein myosin, as well as
elastin and proteoglycan. However,
their relative importance in muscle
protein turnover or muscle disease has
not yet been clarified.
- Language of Publication
- English
- Unique Identifier
- 81089733
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- MeSH Heading (Major)
- Cathepsins|*/AI/IP/ME;
Leukocytes|*EN; Pancreatic
Elastase|*/AI/IP/ME
- MeSH Heading
- Amino Acid Sequence; Human;
Isoenzymes|IP; Molecular Weight;
Proteins|ME
- Publication Type
- JOURNAL ARTICLE; REVIEW
- ISSN
- 0300-5208
- Country of Publication
- NETHERLANDS
Record 4
from database: MEDLINE
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- Title
- Proteoglycan-degrading enzymes. A
radiochemical assay method and the
detection of a new enzyme cathepsin F.
- Author
- Dingle JT; Blow AM; Barrett AJ;
Martin PE
- Address
-
- Source
- Biochem J, 1977 Dec, 167:3, 775-85
- Abstract
- 1. Polyacrylamide beads containing
entrapped 35S-labelled proteoglycan
molecules have been prepared. 2. The
measurement of release of
radioactivity provides an extremely
sensitive assay for proteoglycan-degrading
enzymes, including proteinases and
hyaluronidase. 3. The amount of label
released is a logarithmic function of
enzyme concentration or time of
incubation. Experiments were made in
an attempt to explain this. 4. Assays
were made by the new method at several
pH values, and with the inclusion of
inhibitors to identify the
proteoglycan-degrading enzymes of
rabbit ear cartilage. 5. A previously
undescribed proteinase active against
proteoglycan at pH4.5 but unaffected
by pepstatin, was discovered. The
enzyme was named cathepsin F, and was
partially purified and characterized;
it was detected in human articular
cartilage.
- Language of Publication
- English
- Unique Identifier
- 78103158
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- MeSH Heading (Major)
- Cathepsins|AI/*AN/IP; Proteoglycans|*
- MeSH Heading
- Acrylamides; Animal; Cartilage|EN;
Chromatography, Gel; Human;
Hydrogen-Ion Concentration; IgG;
Pepstatins|PD; Rabbits; Sepharose;
Subcellular Fractions|EN; Sulfur
Radioisotopes; Viscosity
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-2936
- Country of Publication
- ENGLAND
Record 5 from database: MEDLINE
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- Title
- Cathepsin D:
ultra-immunohistochemical localization
in dentinogenesis.
- Author
- Nygren H; Persliden B; Hansson HA;
Linde A
- Address
-
- Source
- Calcif Tissue Int, 1979, 29:3, 251-6
- Abstract
- Cathepsin D was purified from rat
liver using a new affinity
chromatographic method, based on the
coupling to the specific inhibitor
pepstatin. This preparation was used
for the production of specific
antibodies from rabbit. The purified
IgG fraction was conjugated to
horseradish peroxidase in a two-step
coupling procedure and used for
electron microscopic
immunohistochemistry of the
odontoblast-predentine region of the
rat incisor. Precipitates, indicating
the presence of cathepsin D, were seen
in the odontoblast, odontoblast
process, and in the extracellular
unmineralized matrix, the predentine.
The observations are discussed in
relation to proteoglycan degradation
at the mineralization front
simultaneous with crystal formation,
and in relation to the function of
lysosomal enzymes in the turnover of
connective tissue.
- Language of Publication
- English
- Unique Identifier
- 80089530
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- MeSH Heading (Major)
- Cathepsins|*AN/IP; Dentinogenesis|*;
Incisor|*EN/UL; Odontoblasts|*EN/UL
- MeSH Heading
- Animal; Chromatography, Affinity;
Immunoenzyme Techniques; Liver|EN;
Rats
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0171-967X
- Country of Publication
- UNITED STATES
Record 6 from database: MEDLINE
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- Title
- Inhibition of human liver cathepsin
L by alpha 2 cysteine-proteinase
inhibitor and the low-Mr cysteine
proteinase inhibitor from human serum.
- Author
- Pagano M; Esnard F; Engler R;
Gauthier F
- Address
-
- Source
- Biochem J, 1984 May, 220:1, 147-55
- Abstract
- The inhibition of human liver
cathepsin L by two specific proteinase
inhibitors present in human serum,
namely alpha 2 cysteine-proteinase
inhibitor and the low-Mr cysteine-proteinase
inhibitor, was studied. Kinetic
parameters, including inhibition
constants (Ki) and rate constants for
association and dissociation (k+1 and
K-1), were determined. The values
found are consistent with a possible
physiological function of these
inhibitors to control cathepsin L
activity. Furthermore, a transfer of
active proteinase from the complex
with either cysteine-proteinase
inhibitor species to alpha
2-macroglobulin was demonstrated in
vitro. Given the rate of dissociation
of both
cathepsin-L-cysteine-proteinase
inhibitor complexes, a function of
transitory inhibitor can therefore be
hypothesized for these proteins and
might then provide an explanation of
the clearance of lysosomal proteinases.
- Language of Publication
- English
- Unique Identifier
- 84256619
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- MeSH Heading (Major)
- Cathepsins|*AI; Liver|*EN; Protease
Inhibitors|*PD; Sulfhydryl
Compounds|BL/IP/*PD
- MeSH Heading
- Binding Sites; Human; Kinetics;
Lysosomes|EN; Macromolecular Systems
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0264-6021
- Country of Publication
- ENGLAND
Record 7 from database: MEDLINE
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- Title
- Cathepsin B from human renal cortex.
- Author
- Gounaris AD; Slater EE
- Address
-
- Source
- Biochem J, 1982 Aug, 205:2, 295-302
- Abstract
- Cysteine-proteinase activity was
observed in homogenates of
human-cadaver renal cortex. This
activity co-purified with renin
enzymic activity until separation by
aminohexyl-Sepharose--pepstatin
affinity chromatography. The cysteine
proteinase was purified 1780-fold
after the following successive
chromatographic procedures: Sephadex
G-75, DEAE-cellulose DE-52, and an
organomercurial affinity resin. The
proteinase activity was dependent upon
activation by thiol-containing
compounds such as dithiothreitol, as
well as by EDTA, and was inhibited by
the thiol-group-specific alkylating
reagents iodoacetic acid and N-ethylmaleimide.
DE-52 cellulose chromatography
resolved the cysteine proteinase into
two components. On the basis of
molecular size (26 000 daltons),
activity as a function of pH,
stability as a function of pH,
substrate specificity and thermal
lability, the major component (95%)
has been identified as cathepsin B.
The DE-52 cellulose elution pattern of
the minor component (5%) is suggestive
of cathepsin H [Schwartz & Barrett
(1980) Biochem. J. 191, 487-497]
Enzymic activity was determined with
synthetic substrates, in particular
alpha-N-benzoyl-DL-arginine
2-naphthylamide (Bz-Arg-NNap), thus
precluding the detection of cathepsin
L [Kirschke, Langner, Wiederanders,
Ansorge, Bohley & Broghammer
(1976) Acta Biol. Med. Germ. 35,
285-299]. Inhibition by dimethyl
sulphoxide was observed in the
determination of Km = 7.0 +/- 0.4 mM
for the substrate Bz-Arg-NNap, and
care must therefore be taken in the
preparation of substrate solutions.
- Language of Publication
- English
- Unique Identifier
- 83048214
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- MeSH Heading (Major)
- Cathepsins|AI/*IP/*ME; Kidney
Cortex|*EN
- MeSH Heading
- Chromatography, Affinity;
Chromatography, Gel; Chromatography,
Ion Exchange; Dimethyl Sulfoxide|PD;
Electrophoresis, Polyacrylamide Gel;
Human; Substrate Specificity; Support,
Non-U.S. Gov't; Support, U.S. Gov't,
P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-2936
- Country of Publication
- ENGLAND
Record 8 from database: MEDLINE
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- Title
- Specificity and some physical
properties of cathepsin D from bovine
uterus and dental pulp.
- Author
- Schwabe C
- Address
-
- Source
- J Dent Res, 1975 Mar, 54:2, 371-7
- Abstract
- The action of uterine cathepsin D on
the insulin A-chain (S-sulfo) and
porcine glucagon was compared with the
action of bovine dental pulp cathepsin
on the same substrates. Differences
observed with respect to molecular and
catalytic properties suggest that
different gene products (coding for
the same function) are used during
cell differentiation.
- Language of Publication
- English
- Unique Identifier
- 75115257
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- MeSH Heading (Major)
- Cathepsins|*/AN/PD; Dental Pulp|*EN;
Uterus|*EN
- MeSH Heading
- Amino Acids|AN; Animal;
Carbohydrates|AN; Cattle; Chemistry;
Chlorides|PD; Chromatography;
Dithiothreitol|PD; Electrophoresis,
Polyacrylamide Gel; Endonucleases|ME;
Female; Glucagon|ME; Insulin|ME;
Iron|PD; Molecular Weight; Peptide
Fragments|AN/ME; Ribonucleases|ME;
Support, U.S. Gov't, P.H.S.; Swine
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-0345
- Country of Publication
- UNITED STATES
Record 9 from database: MEDLINE
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- Title
- SPI-1-dependent host range of
rabbitpox virus and complex formation
with cathepsin G is associated with
serpin motifs.
- Author
- Moon KB; Turner PC; Moyer RW
- Address
- Department of Molecular Genetics,
University of Florida, Gainesville,
Florida 32610-0266, USA.
- Source
- J Virol, 1999 Nov, 73:11, 8999-9010
- Abstract
- Serpins are a superfamily of serine
proteinase inhibitors which function
to regulate a number of key biological
processes including fibrinolysis,
inflammation, and cell migration.
Poxviruses are the only viruses known
to encode functional serpins. While
some poxvirus serpins regulate
inflammation (myxoma virus SERP1 and
cowpox virus [CPV] crmA/SPI-2) or
apoptosis (myxoma virus SERP2 and CPV
crmA/SPI-2), the function of other
poxvirus serpins remains unknown. The
rabbitpox virus (RPV) SPI-1 protein is
47% identical to crmA and shares all
of the serpin structural motifs.
However, no serpin-like activity has
been demonstrated for SPI-1 to date.
Earlier we showed that RPV with the
SPI-1 gene deleted, unlike wild-type
virus, fails to grow on A549 or PK15
cells (A. Ali, P. C. Turner, M. A.
Brooks, and R. W. Moyer, Virology
202:306-314, 1994). Here we
demonstrate that in the absence of a
functional SPI-1 protein, infected
nonpermissive cells which exhibit the
morphological features of apoptosis
fail to activate terminal caspases or
cleave the death substrates PARP or
lamin A. We show that SPI-1 forms a
stable complex in vitro with cathepsin
G, a member of the chymotrypsin family
of serine proteinases, consistent with
serpin activity. SPI-1 reactive-site
loop (RSL) mutations of the critical
P1 and P14 residues abolish this
activity. Viruses containing the SPI-1
RSL P1 or P14 mutations also fail to
grow on A549 or PK15 cells. These
results suggest that the full virus
host range depends on the serpin
activity of SPI-1 and that in
restrictive cells SPI-1 inhibits a
proteinase with chymotrypsin-like
activity and may function to inhibit a
caspase-independent pathway of
apoptosis.
- Language of Publication
- English
- Unique Identifier
- 99445805
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- MeSH Heading (Major)
- Cathepsins|*ME; Peptides|CH/GE/*ME;
Serine Proteinase Inhibitors|CH/GE/*ME;
Serpins|CH/GE/*ME; Vaccinia Virus|GD/GE/*ME/*PY
- MeSH Heading
- Amino Acid Motifs; Amino Acid
Sequence; Caspases|ME; Cell Line;
Chymotrypsin|AI/ME; Human; Molecular
Sequence Data; Mutagenesis,
Site-Directed; Serine
Endopeptidases|ME; Support, Non-U.S.
Gov't; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-538X
- Country of Publication
- UNITED STATES
Record 10 from database:
MEDLINE
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- Title
- SPI-1-dependent host range of
rabbitpox virus and complex formation
with cathepsin G is associated with
serpin motifs.
- Author
- Moon KB; Turner PC; Moyer RW
- Address
- Department of Molecular Genetics,
University of Florida, Gainesville,
Florida 32610-0266, USA.
- Source
- J Virol, 1999 Nov, 73:11, 8999-9010
- Abstract
- Serpins are a superfamily of serine
proteinase inhibitors which function
to regulate a number of key biological
processes including fibrinolysis,
inflammation, and cell migration.
Poxviruses are the only viruses known
to encode functional serpins. While
some poxvirus serpins regulate
inflammation (myxoma virus SERP1 and
cowpox virus [CPV] crmA/SPI-2) or
apoptosis (myxoma virus SERP2 and CPV
crmA/SPI-2), the function of other
poxvirus serpins remains unknown. The
rabbitpox virus (RPV) SPI-1 protein is
47% identical to crmA and shares all
of the serpin structural motifs.
However, no serpin-like activity has
been demonstrated for SPI-1 to date.
Earlier we showed that RPV with the
SPI-1 gene deleted, unlike wild-type
virus, fails to grow on A549 or PK15
cells (A. Ali, P. C. Turner, M. A.
Brooks, and R. W. Moyer, Virology
202:306-314, 1994). Here we
demonstrate that in the absence of a
functional SPI-1 protein, infected
nonpermissive cells which exhibit the
morphological features of apoptosis
fail to activate terminal caspases or
cleave the death substrates PARP or
lamin A. We show that SPI-1 forms a
stable complex in vitro with cathepsin
G, a member of the chymotrypsin family
of serine proteinases, consistent with
serpin activity. SPI-1 reactive-site
loop (RSL) mutations of the critical
P1 and P14 residues abolish this
activity. Viruses containing the SPI-1
RSL P1 or P14 mutations also fail to
grow on A549 or PK15 cells. These
results suggest that the full virus
host range depends on the serpin
activity of SPI-1 and that in
restrictive cells SPI-1 inhibits a
proteinase with chymotrypsin-like
activity and may function to inhibit a
caspase-independent pathway of
apoptosis.
- Language of Publication
- English
- Unique Identifier
- 99445805
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- MeSH Heading (Major)
- Cathepsins|*ME; Peptides|CH/GE/*ME;
Serine Proteinase Inhibitors|CH/GE/*ME;
Serpins|CH/GE/*ME; Vaccinia Virus|GD/GE/*ME/*PY
- MeSH Heading
- Amino Acid Motifs; Amino Acid
Sequence; Caspases|ME; Cell Line;
Chymotrypsin|AI/ME; Human; Molecular
Sequence Data; Mutagenesis,
Site-Directed; Serine
Endopeptidases|ME; Support, Non-U.S.
Gov't; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-538X
- Country of Publication
- UNITED STATES
Record 11 from database:
MEDLINE
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- Title
- Human lysosomal protective protein
has cathepsin A-like activity distinct
from its protective function.
- Author
- Galjart NJ; Morreau H; Willemsen R;
Gillemans N; Bonten EJ; dAzzo A
- Address
- Department of Cell Biology and
Genetics, Erasmus University,
Rotterdam, The Netherlands.
- Source
- J Biol Chem, 1991 Aug, 266:22,
14754-62
- Abstract
- The protective protein was first
discovered because of its deficiency
in the metabolic storage disorder
galactosialidosis. It associates with
lysosomal beta-galactosidase and
neuraminidase, toward which it exerts
a protective function necessary for
their stability and activity. Human
and mouse protective proteins are
homologous to yeast and plant serine
carboxypeptidases. Here, we provide
evidence that this protein has
enzymatic activity similar to that of
lysosomal cathepsin A: 1)
overexpression of human and mouse
protective proteins in COS-1 cells
induces a 3-4-fold increase of
cathepsin A-like activity; 2) this
activity is reduced to approximately
1% in three galactosialidosis patients
with different clinical phenotypes; 3)
monospecific antibodies raised against
human protective protein precipitate
virtually all cathepsin A-like
activity in normal human fibroblast
extracts. Mutagenesis of the serine
and histidine active site residues
abolishes the enzymatic activity of
the respective mutant protective
proteins. These mutants, however,
behave as the wild-type protein with
regard to intracellular routing,
processing, and secretion. In
contrast, modification of the very
conserved Cys60 residue interferes
with the correct folding of the
precursor polypeptide and, hence, its
intracellular transport and
processing. The secreted active site
mutant precursors, endocytosed by
galactosialidosis fibroblasts, restore
beta-galactosidase and neuraminidase
activities as effectively as wild-type
protective protein. These findings
indicate that the catalytic activity
and protective function of the
protective protein are distinct.
- Language of Publication
- English
- Unique Identifier
- 91317848
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- MeSH Heading (Major)
- beta-Galactosidase|*ME;
Carboxypeptidases|*ME; Cathepsins|*ME;
Glycoproteins|*ME; Lysosomes|EN/*ME
- MeSH Heading
- Amino Acid Sequence; Animal; Cell
Line; Chickens; Fluorescent Antibody
Technique; Human; Immunohistochemistry;
Mice; Microscopy, Immunoelectron;
Molecular Sequence Data; Mutagenesis,
Site-Directed; Neuraminidase|ME;
Sequence Alignment; Transfection
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9258
- Country of Publication
- UNITED STATES
Record 12 from database:
MEDLINE
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- Title
- Expression of rat cathepsin D cDNA
in Saccharomyces cerevisiae:
implications for intracellular
targeting of cathepsin D to vacuoles.
- Author
- Nishimura Y; Takeshima H; Sakaguchi
M; Mihara K; Omura T; Kato K; Himeno M
- Address
- Division of Physiological Chemistry,
Faculty of Pharmaceutical Sciences,
Kyushu University, Fukuoka.
- Source
- J Biochem (Tokyo), 1995 Jul, 118:1,
168-77
- Abstract
- To investigate the intracellular
transport mechanisms of lysosomal
cathepsin D in yeast cells, we
produced cathepsin D in Saccharomyces
cerevisiae by placing the coding
region under the control of the
promoter of the yeast
glyceraldehyde-3-phosphate
dehydrogenase (GAPDH) gene.
Immunoblotting analysis by the use of
an antibody specific for rat cathepsin
D coding sequence produced an
intermediate species which had a
slightly higher molecular weight than
that of the mature cathepsin D. Cell
fractionation experiments demonstrated
that the cathepsin D polypeptide was
colocalized to the yeast vacuoles with
the marker enzyme carboxypeptidase Y
in a Ficoll step gradient. A
biosynthesis study with pulse-chase
kinetic analysis revealed that the
precursor polypeptide was accurately
sorted to the yeast vacuoles as
determined by cell fractionation, and
that N-linked carbohydrate
modifications were not required for
vacuolar sorting of this protein. To
elucidate the role of the propeptide
region of cathepsin D, which might
function in the intracellular
targeting to the vacuole, a deletion
mutant of cathepsin D lacking the
propeptide was prepared and its
intracellular targeting was examined
after transfection into yeast cells.
Immunoblotting analysis demonstrated
that the propeptide-deleted mutant
protein was recovered in a low
quantity as compared with that in the
case of yeast cells expressing the
wild-type protein in the isolated
vacuolar fraction. Immunofluorescence
analysis revealed that the deletion
mutant protein appeared to be
accumulated within the intracellular
small vesicles but not in the
carboxypeptidase Y-positive vacuoles.
Overall, these results indicate that
the rat cathepsin D precursor
polypeptide is recognized by
mechanisms similar to those involved
in the intracellular sorting of
vacuolar proteins through the ER/Golgi/vacuolar
sorting pathway in yeast cells, and
that the propeptide has an important
function in translocation of the
cathepsin D polypeptide to the
vacuole.
- Language of Publication
- English
- Unique Identifier
- 96015165
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- MeSH Heading (Major)
- Cathepsin D|BI/*GE; DNA,
Complementary|*BI; Promoter Regions
(Genetics)|*; Vacuoles|*DE/GE
- MeSH Heading
- Animal; Biological Transport;
Fluorescent Antibody Technique,
Indirect; Gene Deletion; Glycosylation;
Mutation; Rats; Recombinant
Proteins|BI; Saccharomyces cerevisiae;
Support, Non-U.S. Gov't;
Tunicamycin|PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-924X
- Country of Publication
- JAPAN
Record 13 from database:
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- Title
- The expression and function of
cystatin C and cathepsin B and
cathepsin L during mouse embryo
implantation and placentation.
- Author
- Afonso S; Romagnano L; Babiarz B
- Address
- Department of Cell, Developmental
and Neurobiology, Nelson Labs, Busch
Campus, Rutgers University,
Piscataway, NJ 08855, USA. afonso@rci.rutgers.edu
- Source
- Development, 1997 Sep, 124:17,
3415-25
- Abstract
- The implantation of the mouse embryo
requires the controlled invasion of
the uterine stroma by the embryonic
trophoblast. This event is dependent,
in part, on the secretion of matrix
metalloproteinases and serine
proteinases for the extracellular
degradation of the uterine matrix.
Proteinase activity is controlled by
stromal decidualization and specific
proteinase inhibitors. This work adds
to our understanding of implantation
and placentation by reporting the
expression and function of another
class of proteinases/inhibitors
closely related to invasive cell
behavior. We focused on the cysteine
proteinases, cathepsins B and L, and
their inhibitor cystatin C. Northern
blots showed that trophoblast
expressed cathepsin B throughout the
invasive period (days 5.5-10.5). Both
cathepsin B message and cathepsin L
protein were localized to the mature,
invasive trophoblast giant cells.
Substrate gel electrophoresis showed
an increase in giant cell cathepsin
activity with enzyme profiles changing
at the end of the invasive period.
Northern and western blotting showed
that cystatin C, the main inhibitor of
cathepsins, was a major product of the
decidualizing stroma. Message levels
first increased in peripheral
decidualizing cells, with the protein
localizing close to the embryo during
implantation (days 5.5-8.5). With the
regression of the decidua beginning on
day 9.5, a coordinated upregulation of
both cathepsin B and cystatin C was
observed implying a role for
controlled cathepsin expression during
apoptosis. E-64, a synthetic inhibitor
of cathepsins B and L, was injected
into pregnant females at the stage of
blastocyst attachment (days 4.5-5.5).
High doses resulted in the complete
failure of implantation while lower
doses resulted in stunted embryos and
a reduced decidual reaction. These
results suggested that cathepsins B
and L are necessary for normal embryo
development and uterine
decidualization, and that decidua
contributes to their control by a
coordinated expression of cystatin C
within the implantation site.
- Language of Publication
- English
- Unique Identifier
- 97454261
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- MeSH Heading (Major)
- Cathepsin B|AI/*GE/*PH;
Cathepsins|AI/*GE/*PH; Cystatins|*GE/*PH;
Ovum Implantation|DE/*GE/*PH;
Placentation|DE/*GE/*PH
- MeSH Heading
- Animal; Cysteine Proteinase
Inhibitors|PD; Decidua|ME; Female;
Gene Expression; In Situ
Hybridization; Leucine|AA/PD; Male;
Mice; Pregnancy; RNA, Messenger|GE/ME;
Support, Non-U.S. Gov't; Support, U.S.
Gov't, P.H.S.; Trophoblast|ME
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0950-1991
- Country of Publication
- ENGLAND
Record 14 from database:
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- Title
- Comparative effects of cathepsin
inhibitors on rat embryonic
development in vitro. Evidence that
cathepsin D is unimportant in the
proteolytic function of yolk sac.
- Author
- Freeman SJ; Brown NA
- Address
-
- Source
- J Embryol Exp Morphol, 1985 Apr,
86:, 271-81
- Abstract
- The effects of two proteinase
inhibitors, leupeptin and pepstatin on
the development of 9.5-day rat
conceptuses in vitro has been studied.
All cultures were of 48 h duration and
the inhibitors were present throughout
the entire period. When pepstatin was
added to the culture medium (5-25
micrograms/ml) conceptuses developed
and grew to an extent that did not
differ from untreated controls.
However, leupeptin (1-4 micrograms/ml)
caused severe growth retardation and
abnormal development of conceptuses.
The effects of the two inhibitors on
the hydrolysis of 125I-labelled BSA
and haemoglobin by homogenates of
10.5-day yolk sac indicated the
biochemical basis for the differential
toxic effects of the two inhibitors on
development. Leupeptin was highly
inhibitory of the degration of both
substrates whereas pepstatin caused no
inhibition of 125I-labelled BSA
hydrolysis, and only a slight
inhibition of haemoglobin hydrolysis.
These observations demonstrate that
cathepsin D, a lysosomal aspartic
proteinase that is specifically
inhibited by pepstatin is not involved
in yolk-sac-mediated protein
utilization by early organogenesis-phase
conceptuses and that lysosomal
cysteine proteinases, specifically
inhibited by leupeptin, are of
paramount importance in this yolk sac
function.
- Language of Publication
- English
- Unique Identifier
- 85291486
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- MeSH Heading (Major)
- Cathepsins|*AI; Fetal
Development|*DE; Yolk Sac|*ME
- MeSH Heading
- Animal; Cathepsin D|ME; Cells,
Cultured; Comparative Study;
Hemoglobins|ME; Hydrogen-Ion
Concentration; Leupeptins|PD;
Pepstatins|PD; Rats; Rats, Inbred
Strains; Serum Albumin, Bovine|ME;
Time Factors
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-0752
- Country of Publication
- ENGLAND
Record 15 from database:
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- Title
- Immunocytochemical studies of
cathepsin D in human skeletal muscle.
- Author
- Whitaker JN; Bertorini TE; Mendell
JR
- Address
-
- Source
- Ann Neurol, 1983 Feb, 13:2, 133-42
- Abstract
- The distribution of cathepsin D, an
acidic endopeptidase, was localized by
immunocytochemistry in human skeletal
muscle obtained from 34 persons with a
variety of neuromuscular disorders.
Normal human skeletal muscle contained
small amounts of cathepsin D, all of
which was found close to the
sarcolemmal membrane. Immunoreactive
cathepsin D was present in the
cytoplasm of many infiltrating
phagocytic cells and was increased in
skeletal muscle fibers from patients
with muscular dystrophies,
inflammatory myopathies,
rhabdomyolysis, acid maltase
deficiency, and neurogenic atrophy. In
cases of Duchenne type muscular
dystrophy, the increase in cathepsin D
was especially prominent in small
regenerating fibers, in which it was
visualized at the ultrastructural
level in lysosome-like organelles and
extralysosomal locations. The function
of cathepsin D in skeletal muscle is
unclear, but the present findings
suggest a possible role in muscle
regeneration and repair. Such a role
would necessitate careful selection of
drugs which interfere with proteolytic
activity if they are to be used as
therapeutic agents in treating
neuromuscular diseases.
- Language of Publication
- English
- Unique Identifier
- 83151354
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- MeSH Heading (Major)
- Cathepsins|*IM; Immunologic
Techniques|*; Muscles|*AN/UL
- MeSH Heading
- Adolescence; Antibodies|AN; Child;
Histocytochemistry; Human; Male;
Muscular Diseases|ME/PA; Muscular
Dystrophies|ME; Neuromuscular
Diseases|ME; Support, U.S. Gov't,
Non-P.H.S.; Tissue Distribution
- Publication Type
- JOURNAL ARTICLE
- Country of Publication
- UNITED STATES
Record 16 from database:
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- Title
- Changes in sciatic nerve cathepsin D
after ligation or exposure to
neurotoxins.
- Author
- Whitaker JN; Dodd SP; Sahenk Z;
Mendell JR
- Address
-
- Source
- J Neuropathol Exp Neurol, 1983 Jan,
42:1, 87-98
- Abstract
- The content and distribution of
cathepsin D, a lysosomal acidic
endopeptidase, were determined by
immunochemical methods in rat sciatic
nerve near the site of a ligature or
after exposure of animals to
neurotoxins. In normal sciatic nerve,
cathepsin D was localized
predominantly in the perinuclear
regions of Schwann cells. In ligated
nerve, cathepsin D increased equally
in both the proximal and distal nerve
segments adjacent to the ligature.
Although orthograde and retrograde
axonal transport of cathepsin D may
have contributed to this increase,
immunocytochemical methods indicated
that Schwann cells or other phagocytic
cells accounted for the bulk of the
increased cathepsin D content of
nerve. Axonal function was
nontraumatically altered by the
administration of 2,5-hexanedione,
acrylamide, B,B'-iminodipropionitrile
or zinc pyridinethione. Exposure to
any of these neurotoxins raised
cathepsin D content throughout the
sciatic nerve twofold or more, and
greater amounts of immunoreactive
cathepsin D in the cytoplasm of
Schwann cells could be demonstrated
immunocytochemically. These results
indicate that changes in cathepsin D
content of Schwann cells may be a
reflection of their catabolic
activity. The increased Schwann cell
cathepsin D content in toxic
axonopathies is further proof for an
enhanced Schwann cell role as a
phagocyte resulting from axonal
injury.
- Language of Publication
- English
- Unique Identifier
- 83111068
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- MeSH Heading (Major)
- Cathepsins|*AN/PH; Sciatic
Nerve|*AN/DE/PH/UL
- MeSH Heading
- Animal; Axonal Transport|DE;
Ligation; Male; Neurotoxins|PD; Rats;
Rats, Inbred Strains; Support,
Non-U.S. Gov't; Support, U.S. Gov't,
Non-P.H.S.; Support, U.S. Gov't,
P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-3069
- Country of Publication
- UNITED STATES
Record 17 from database:
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- Title
- Effects of cathepsin G pretreatment
of platelets on their subsequent
responses to aggregating agents.
- Author
- Kinlough Rathbone RL; Perry DW; Rand
ML; Packham MA
- Address
- Department of Pathology and
Molecular Medicine, McMaster
University, Hamilton, Ontario, Canada.
- Source
- Thromb Res, 1999 Sep, 95:6, 315-23
- Abstract
- Cathepsin G, a proteolytic enzyme
from activated leukocytes, can
interact with platelets during
inflammation and thrombosis. Platelets
that have been exposed to cathepsin G
in thrombi may recirculate if they are
freed during fibrinolysis. To
determine whether some of the
subsequent functions of such platelets
would be impaired, we investigated the
responses of cathepsin G-pretreated
platelets to agonists that they would
encounter in the circulation.
Suspensions of washed human platelets
were labeled with [14C]serotonin and
resuspended in Tyrode-albumin solution
(with 2 mM Ca2+ and apyrase). After 15
minute incubation with 400 nM
cathepsin G at 37 degrees C, 52+/-3%
of [14C]serotonin had been released,
and glycoprotein Ib was degraded. The
platelets were washed and resuspended
in fresh medium to remove cathepsin G
and released materials. Ristocetin-induced
agglutination was abolished,
indicating that the binding site for
von Willebrand Factor on glycoprotein
Ib had been removed. Aggregation and
release of residual [14C]serotonin in
response to 0.1-1.0 U/mL thrombin was
blocked or greatly reduced by the
cathepsin G pretreatment. This
inhibition is probably largely due to
cleavage by cathepsin G of some of the
protease-activated receptors at the
C-terminal side of Ser42 so that the
tethered ligand is lost. Pretreatment
with cathepsin G did not affect
responses to ADP or a low
concentration of platelet-activating
factor in the presence of fibrinogen,
indicating that receptors for these
agonists were unaffected and that the
function of the fibrinogen receptor,
GPIIb/IIIa was unchanged. Responses to
cathepsin G, the thrombin
receptor-activating peptide SFLLRN,
collagen, or the thromboxane A2
mimetic U46619 were partially
inhibited, even in the presence of
added fibrinogen. Platelet adhesion to
a collagen-coated surface was 51+/-7%
inhibited, which may indicate cleavage
of a collagen receptor or receptors;
this may partly account for strong
inhibition of collagen-induced
aggregation and release of granule
contents; additionally, as shown by
inhibition of responses to U46619, the
function of the thromboxane A2
receptor may be compromised. Thus,
although cathepsin G activates
platelets, if they recirculate after
interaction with it, their subsequent
adhesion to damaged vessel walls,
aggregation, and release of granule
contents induced by thrombin and
collagen will be diminished.
- Language of Publication
- English
- Unique Identifier
- 99454533
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- MeSH Heading (Major)
- Antibiotics, Peptide|*PD; Cathepsins|*PD;
Platelet Aggregation|*DE; Ristocetin|*PD
- MeSH Heading
- Adenosine Diphosphate|PD; Blood
Platelets|ME/PA; Drug Interactions;
Hemostatics|PD; Human; Platelet
Activating Factor|PD; Platelet
Glycoprotein GPIb-IX Complex|ME;
Serotonin|ME; Support, Non-U.S. Gov't;
Thrombin|PD; Vasoconstrictor Agents|PD;
15-Hydroxy-11 alpha,9
alpha-(epoxymethano)prosta-5,13-dienoic
Acid|PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0049-3848
- Country of Publication
- UNITED STATES
Record 18 from database:
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- Title
- Effects of cathepsin G pretreatment
of platelets on their subsequent
responses to aggregating agents.
- Author
- Kinlough Rathbone RL; Perry DW; Rand
ML; Packham MA
- Address
- Department of Pathology and
Molecular Medicine, McMaster
University, Hamilton, Ontario, Canada.
- Source
- Thromb Res, 1999 Sep, 95:6, 315-23
- Abstract
- Cathepsin G, a proteolytic enzyme
from activated leukocytes, can
interact with platelets during
inflammation and thrombosis. Platelets
that have been exposed to cathepsin G
in thrombi may recirculate if they are
freed during fibrinolysis. To
determine whether some of the
subsequent functions of such platelets
would be impaired, we investigated the
responses of cathepsin G-pretreated
platelets to agonists that they would
encounter in the circulation.
Suspensions of washed human platelets
were labeled with [14C]serotonin and
resuspended in Tyrode-albumin solution
(with 2 mM Ca2+ and apyrase). After 15
minute incubation with 400 nM
cathepsin G at 37 degrees C, 52+/-3%
of [14C]serotonin had been released,
and glycoprotein Ib was degraded. The
platelets were washed and resuspended
in fresh medium to remove cathepsin G
and released materials. Ristocetin-induced
agglutination was abolished,
indicating that the binding site for
von Willebrand Factor on glycoprotein
Ib had been removed. Aggregation and
release of residual [14C]serotonin in
response to 0.1-1.0 U/mL thrombin was
blocked or greatly reduced by the
cathepsin G pretreatment. This
inhibition is probably largely due to
cleavage by cathepsin G of some of the
protease-activated receptors at the
C-terminal side of Ser42 so that the
tethered ligand is lost. Pretreatment
with cathepsin G did not affect
responses to ADP or a low
concentration of platelet-activating
factor in the presence of fibrinogen,
indicating that receptors for these
agonists were unaffected and that the
function of the fibrinogen receptor,
GPIIb/IIIa was unchanged. Responses to
cathepsin G, the thrombin
receptor-activating peptide SFLLRN,
collagen, or the thromboxane A2
mimetic U46619 were partially
inhibited, even in the presence of
added fibrinogen. Platelet adhesion to
a collagen-coated surface was 51+/-7%
inhibited, which may indicate cleavage
of a collagen receptor or receptors;
this may partly account for strong
inhibition of collagen-induced
aggregation and release of granule
contents; additionally, as shown by
inhibition of responses to U46619, the
function of the thromboxane A2
receptor may be compromised. Thus,
although cathepsin G activates
platelets, if they recirculate after
interaction with it, their subsequent
adhesion to damaged vessel walls,
aggregation, and release of granule
contents induced by thrombin and
collagen will be diminished.
- Language of Publication
- English
- Unique Identifier
- 99454533
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- MeSH Heading (Major)
- Antibiotics, Peptide|*PD; Cathepsins|*PD;
Platelet Aggregation|*DE; Ristocetin|*PD
- MeSH Heading
- Adenosine Diphosphate|PD; Blood
Platelets|ME/PA; Drug Interactions;
Hemostatics|PD; Human; Platelet
Activating Factor|PD; Platelet
Glycoprotein GPIb-IX Complex|ME;
Serotonin|ME; Support, Non-U.S. Gov't;
Thrombin|PD; Vasoconstrictor Agents|PD;
15-Hydroxy-11 alpha,9
alpha-(epoxymethano)prosta-5,13-dienoic
Acid|PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0049-3848
- Country of Publication
- UNITED STATES
Record 19 from database:
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- Title
- Effects of cell density and cell
proliferation on acid cholesterol
esterase and cathepsin activity of
cultured human skin fibroblasts.
- Author
- Kenagy RD; Bierman EL
- Address
-
- Source
- Biochim Biophys Acta, 1983 Nov,
754:2, 174-80
- Abstract
- We tested the effects of fibroblast
cell density and proliferation on the
activities of acid cholesterol
esterase and cathepsins, the lysosomal
enzymes which degrade low-density
lipoprotein. Rates of cell
proliferation were increased by: (1)
fibroblast conditioned medium, (2)
increasing the time since subculture
from 3 to 7 days, and (3) decreasing
the plating density of cells.
Cathepsin activity was consistently
decreased as cellular proliferation
was increased by these various
methods. Changes in acid cholesterol
esterase activity were more variable.
For example, acid cholesterol esterase
activity was consistently a positive
function of cell density only at
densities under 3 micrograms
protein/cm2, while cathepsin activity
increased up to densities of 16
micrograms protein/cm2. However, the
activities of both enzymes were lower
at cell densities of under 3
micrograms cell protein/cm2 compared
to confluent cultures. Sparse
fibroblast cultures may provide a
unique model system to study
low-density lipoprotein metabolism
since, at low cell density, LDL
receptor activity is high while
lysosomal activity is low, making it
possible that lysosomal degradation
could become the rate-limiting step in
the process of LDL degradation rather
than receptor-mediated internalization
of the lipoprotein. This might then
allow an accumulation of
lipoprotein-derived cholesteryl esters
in the cell. Such a model could be
relevant to the propensity of arterial
cells to become foam cells during
atherogenesis.
- Language of Publication
- English
- Unique Identifier
- 84080495
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- MeSH Heading (Major)
- Carboxylic Ester Hydrolases|*ME;
Cathepsins|*ME; Cholesterol
Esterase|*ME; Receptors, Cell
Surface|*PD; Skin|*EN
- MeSH Heading
- Cell Count; Cell Division; Cells,
Cultured; Fibroblasts|EN; Human;
Hydrogen-Ion Concentration;
Lipoproteins, LDL|ME; Lysosomes|EN;
Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-3002
- Country of Publication
- NETHERLANDS
Record 20 from database:
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- Title
- Identification and characterization
of the Cydia pomonella granulovirus
cathepsin and chitinase genes.
- Author
- Kang W; Tristem M; Maeda S; Crook
NE; OReilly DR
- Address
- Department of Biology, Imperial
College of Science, Technology and
Medicine, London, UK.
- Source
- J Gen Virol, 1998 Sep, 79 ( Pt 9):,
2283-92
- Abstract
- A 3.2 kb BamHI-EcoRI fragment of the
Cydia pomonella granulovirus (CpGV)
genome was subcloned and
characterized. Sequence analysis
revealed two complete and one partial
open reading frames (ORFs). ORF7L is
predicted to encode a 66.7 kDa protein
(594 amino acid residues) that is 57%
identical (amino acid sequence) to the
chiA gene (ORF126) of Autographa
californica nucleopolyhedrovirus (AcMNPV),
encoding a chitinase. ORF8R is 333
amino acids in length and shows high
similarity (between 64% and 67%) with
baculovirus cathepsins. The partial
ORF, ORF5L, is related to AcMNPV
ORF145 of unknown function.
Phylogenetic trees were constructed
for both chitinase and cathepsin
sequences from baculoviruses and other
species. In both cases, the
baculovirus sequences were
monophyletic but with a deep division
between the GVs and NPVs, suggesting
both genes were present in an
ancestral virus prior to the
separation of the two genera. However,
these studies did not provide
definitive evidence for the origin of
either protein in baculoviruses. To
investigate CpGV cathepsin function, a
rescue experiment was performed using
a Bombyx mori NPV (BmNPV) mutant (BmCysPD)
which lacks a functional cathepsin (cath)
gene. Larvae infected with
BmCysPD-Cp.cat, a BmCysPD derivative
carrying CpGV cath, showed similar
symptoms to wild-type BmNPV infected
insects, confirming that CpGV cath
encodes a functional cathepsin. Primer
extension analysis of mRNA from
BmCysPD-Cp.cat infected cells showed
that CpGV cath transcription was
initiated from a consensus late
transcription motif (ATAAG) within the
CpGV sequences, indicating that a CpGV
late promoter motif was recognized in
this NPV system.
- Language of Publication
- English
- Unique Identifier
- 98418511
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- MeSH Heading (Major)
- Baculoviridae|*EN/*GE/PY; Cathepsins|*GE;
Chitinase|*GE; Genes, Viral|*;
Moths|*VI
- MeSH Heading
- Amino Acid Sequence; Animal; Base
Sequence; Cell Line; Cysteine
Endopeptidases|GE; DNA, Viral|GE;
Larva|VI; Molecular Sequence Data;
Open Reading Frames; Phylogeny;
Recombination, Genetic; Restriction
Mapping; Sequence Homology, Amino
Acid; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-1317
- Country of Publication
- ENGLAND
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- Title
- Effects of human neutrophil elastase
and cathepsin G on the reactivity of
platelets with antiplatelet
antibodies.
- Author
- Bykowska K; Maslanka K; Uhrynowska
M; Kopec M; Lopaciuk S
- Address
- Laboratory or Blood Coagulation and
Hemostasis, Institute of Hematology
and Blood Transfusion, Warsaw.
- Source
- Acta Haematol Pol, 1995, 26:2,
163-70
- Abstract
- Two human neutrophil serine
proteases, elastase (HNE) and
cathepsin G (CathG), are known to
change the structure and hemostatic
function of platelet surface membrane.
The platelet membrane contains
glycoproteins (GPs) which function as
alloantigens, autoantigens and targets
of drug-induced antibodies. The aim of
this study was to investigate whether
proteolysis of platelet GPs by HNE and
CathG is associated with changes in
the reactivity of platelets to
antiplatelet antibodies. The platelet
immunoreactivity was examined using
the MAIPA (monoclonal
antibody-specific immobilization of
platelet antigens) assay and PSIFT
(platelet suspension
immunofluorescence test). The
treatment of platelets with HNE led to
a moderate increase in their
reactivity to quinidine-dependent
(anti-GP Ib) antibody and to a slight
decline in the expression of HPA-1a.
In contrast, CathG did not provoke any
significant changes in platelet
reactions with quinidine dependent and
anti-HPA-1a antibodies. Both enzymes
had no significant effect on the
expression of HLA-A2, HLA-A3, HLA-B7
and HLA-B8 on platelets.
- Language of Publication
- English
- Unique Identifier
- 95381743
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- MeSH Heading (Major)
- Antibodies|*IM; Blood Platelets|*IM;
Cathepsins|*ME; Pancreatopeptidase|*ME;
Platelet Membrane Glycoproteins|*ME;
Serine Proteinases|*ME
- MeSH Heading
- Fluorescent Antibody Technique;
Human; Immunoblotting; In Vitro
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0001-5814
- Country of Publication
- POLAND
Record 22 from database:
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- Title
- The atomic model of the human
protective protein/cathepsin A
suggests a structural basis for
galactosialidosis.
- Author
- Rudenko G; Bonten E; Hol WG; dAzzo A
- Address
- Department of Biological Structure,
Howard Hughes Medical Institute,
University of Washington, Seattle
98195-7742, USA.
- Source
- Proc Natl Acad Sci U S A, 1998 Jan,
95:2, 621-5
- Abstract
- Human protective protein/cathepsin A
(PPCA), a serine carboxypeptidase,
forms a multienzyme complex with beta-galactosidase
and neuraminidase and is required for
the intralysosomal activity and
stability of these two glycosidases.
Genetic lesions in PPCA lead to a
deficiency of beta-galactosidase and
neuraminidase that is manifest as the
autosomal recessive lysosomal storage
disorder galactosialidosis. Eleven
amino acid substitutions identified in
mutant PPCAs from clinically different
galactosialidosis patients have now
been modeled in the three-dimensional
structure of the wild-type enzyme. Of
these substitutions, 9 are located in
positions likely to alter drastically
the folding and stability of the
variant protein. In contrast, the
other 2 mutations that are associated
with a more moderate clinical outcome
and are characterized by residual
mature protein appeared to have a
milder effect on protein structure.
Remarkably, none of the mutations
occurred in the active site or at the
protein surface, which would have
disrupted the catalytic activity or
protective function. Instead, analysis
of the 11 mutations revealed a
substantive correlation between the
effect of the amino acid substitution
on the integrity of protein structure
and the general severity of the
clinical phenotype. The high incidence
of PPCA folding mutants in
galactosialidosis reflects the fact
that a single point mutation is
unlikely to affect both the beta-galactosidase
and the neuraminidase binding sites of
PPCA at the same time to produce the
double glycosidase deficiency.
Mutations in PPCA that result in
defective folding, however, disrupt
every function of PPCA simultaneously.
- Language of Publication
- English
- Unique Identifier
- 98118562
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- MeSH Heading (Major)
- Carboxypeptidases|*CH/GE/ME;
Lysosomal Storage Diseases|GE/*ME;
Models, Molecular|*
- MeSH Heading
- Human; Mutation; Support, Non-U.S.
Gov't; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0027-8424
- Country of Publication
- UNITED STATES
Record 23 from database:
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- Title
- Localization of cathepsin B in
normal and hyperplastic human prostate
by immunoperoxidase and protein A-gold
techniques.
- Author
- Sinha AA; Gleason DF; Limas C; Reddy
PK; Wick MR; Hagen KA; Wilson MJ
- Address
- Veterans Administration Medical
Center Research Service, Minneapolis,
Minnesota 55417.
- Source
- Anat Rec, 1989 Mar, 223:3, 266-75
- Abstract
- Cathepsin B, a lysosomal cysteine
protease, was localized in normal
prostate and benign prostatic
hyperplasia (BPH) using
immunoperoxidase and protein A-gold
techniques. Our objective was to
determine whether cathepsin B was
involved in the prostatic epithelium
affected by nodular hyperplasia. All
samples were collected immediately
after prostatectomy.
Immunohistochemical studies showed
that the enzyme was expressed in the
supranuclear cytoplasm of columnar
cells and in numerous basal cells of
normal and BPH acini. The strongest
localization of cathepsin B occurred
in acinar basal cells; hence, it is
possible that cathepsin B could be
useful as a marker for such cellular
elements. Stromal macrophages showed
reaction products, but lymphocytes and
neutrophils did not. In both normal
and hyperplastic glands, the enzyme
was localized by gold particles in
lysosomes, secretory granules, and
vacuoles of columnar epithelial acinar
cells. Immunoelectron microscopic
study also showed the presence of
cathepsin B in the heterochromatin
(condensed chromatin) and nuclear
membranes of columnar and basal cells,
but not in euchromatin or nucleoli. At
present, the function of cathepsin B
in the nuclei of basal and columnar
cells remains unknown. However, the
cathepsin B in the cytoplasmic
compartment might be associated with
the lysosomal function of the cells.
The role of cathepsin B as a marker
for basal cell participation in the
development of prostatic lesions
should be studied further.
- Language of Publication
- English
- Unique Identifier
- 89164840
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- MeSH Heading (Major)
- Cathepsin B|IM/*ME; Prostate|*ME/PA
- MeSH Heading
- Gold|DU; Human; Hyperplasia; Immune
Sera|IM; Immunoenzyme Techniques;
Male; Reference Values; Staphylococcal
Protein A|DU; Support, Non-U.S. Gov't;
Support, U.S. Gov't, Non-P.H.S.;
Tissue Distribution
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0003-276X
- Country of Publication
- UNITED STATES
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- Title
- Progesterone and estrogen control of
the response of rat uterine lysosomal
cathepsin D activity to a deciduogenic
stimulus.
- Author
- Moulton BC
- Address
-
- Source
- Endocrinology, 1982 Apr, 110:4,
1197-202
- Abstract
- Endometrial sensitization to
deciduogenic stimuli and destruction
of luminal epithelial cells during the
uterine decidual reaction may depend
upon the control of endometrial
lysosome function by progesterone and
estradiol. These experiments examined
progesterone and estrogen control of
the levels of uterine cathepsin D and
the response of cathepsin D activity
to a deciduogenic stimulus. The
progestin medroxyprogesterone acetate
increased rates of uterine cathepsin D
synthesis, but these rates were not
enhanced by estradiol pretreatment.
The response of cathepsin D activity
to a deciduogenic stimulus, however,
required progestin pretreatment,
followed by estrogen treatment.
Decreases in cathepsin D activity
after a deciduogenic stimulus required
estrogen stimulation for approximately
12 h, and this estrogen effect could
be suppressed by treatment with
dexamethasone or inhibitors of
prostanoid synthesis. These results
indicate that destruction of luminal
epithelial cells during the uterine
decidual reaction involves the
coordinated control of the cathepsin D
content by progesterone and of
intracellular lysosome activity by
estradiol.
- Language of Publication
- English
- Unique Identifier
- 82138551
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- MeSH Heading (Major)
- Cathepsins|*ME; Decidua|*PH;
Estrogens|*PD; Lysosomes|*EN;
Progesterone|*PD; Uterus|*EN
- MeSH Heading
- Animal; Castration; Dexamethasone|PD;
Estradiol|PD; Estriol|PD; Female;
Meclofenamic Acid|PD;
Medroxyprogesterone|AA/PD;
Pseudopregnancy|EN; Rats; Support,
U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0013-7227
- Country of Publication
- UNITED STATES
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- Title
- Urine activity of cathepsin B,
collagenase and urine excretion of TGF-beta
1 and fibronectin in membranous
glomerulonephritis.
- Author
- Senatorski G; Paczek L; Su…owicz
W; Gradowska L; Bart…omiejczyk I
- Address
- Department of Immunotherapy, Medical
University of Warsaw, Poland.
- Source
- Res Exp Med (Berl), 1998 Dec, 198:4,
199-206
- Abstract
- In 30% of cases nephrotic syndrome
is caused by membranous
glomerulonephritis (MG). Protein
accumulation in glomeruli leads to
progressive loss of kidney function
and damage of structure in MG. The
role of tissue proteolytic systems and
growth factors in this process is not
known. The purpose of the study was to
estimate urine cathepsin B,
collagenase activity and urine
excretion of TGF-beta 1 and
fibronectin in MG. Cathepsin B
activity was greater in the urine of
MG patients than in the control group
(10.58 +/- 8.73 pmol AMC/mg creatinine
per min-1 vs control 7.11 +/- 2.05
pmol AMC/mg creatinine per min-1; P
< 0.05). Urine collagenase activity
was higher in the group of patients
than in the control group (8.59 +/-
4.26 pmol AMC/mg creatinine per min-1
vs control 3.84 +/- 2.09 pmol AMC/mg
creatinine per min-1 P < 0.02).
Urine excretion of fibronectin (45.60
ng/mg creatinine vs control 10.30 ng/mg
creatinine; P < 0.04) and TGF-beta
1 levels in the urine were higher than
in controls (283.55 +/- 248.13 pg/ml
vs 36.11 +/- 48.01 pg/ml; P <
0.01). Results suggest glomerular
overproduction of TGF-beta 1 and
urinary leak of proteolytic enzymes
(PE). This may result in decreased
glomerular PE activity in MG and, with
time, may lead to protein accumulation
in renal glomeruli and to progressive
loss of kidney function and damage of
structures as the course of MG
progresses. PE urine composition as
well as ECM protein and cytokine urine
excretion may allow noninvasive
glomerulopathy course monitoring in
humans in the future.
- Language of Publication
- English
- Unique Identifier
- 99095671
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- MeSH Heading (Major)
- Cathepsin B|*UR; Collagenases|*UR;
Fibronectins|*UR; Glomerulonephritis,
Membranous|*UR; Transforming Growth
Factor beta|BL/*UR
- MeSH Heading
- Adult; Female; Human; Male; Middle
Age
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0300-9130
- Country of Publication
- GERMANY
Record 26 from database:
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- Title
- Structures at the proteolytic
processing region of cathepsin D.
- Author
- Yonezawa S; Takahashi T; Wang XJ;
Wong RN; Hartsuck JA; Tang J
- Address
- Laboratory of Protein Studies,
Oklahoma Medical Research Foundation,
Oklahoma City.
- Source
- J Biol Chem, 1988 Nov, 263:31,
16504-11
- Abstract
- The amino acid sequences at the
"proteolytic processing
regions" of cathepsin Ds have
been determined for the enzymes from
cows, pigs, and rats in order to
deduce the sites of cleavage as well
as the function of the proteolytic
processing of cathepsin D. For bovine
cathepsin D, the "processing
region" sequence was determined
from a peptide isolated from the
single-chain enzyme. The COOH-terminal
sequence of the light chain and the
NH2-terminal sequence of the heavy
chain were also determined. The
processing region sequence of porcine
cathepsin D was determined from its
cDNA structure, and the same structure
from rat cathepsin D was determined
from the peptide sequence of the
single-chain rat enzyme. From sequence
homology to other aspartic proteases
whose x-ray crystallographic
structures are known, such as
pepsinogen and penicillopepsin, it is
clear that the processing regions are
insertions to form an extended
beta-hairpin loop between residues 91
and 92 (porcine pepsin numbers).
However, the sizes of the processing
regions of cathepsin Ds from different
species are considerably different.
For the enzymes from rats, cows, pigs,
and human, the sizes of the processing
regions are 6, 9, 9, and 11 amino acid
residues, respectively. The amino acid
sequences within the processing
regions are considerably different. In
addition, the proteolytic processing
sites were found to be completely
different in the bovine and porcine
cathepsin Ds. While in the porcine
enzyme, an Asn-Ser bond and a Gly-Val
bond are cleaved to release 5 residues
as a consequence of the processing; in
the bovine enzyme, two Ser-Ser bonds
are cleaved to release 2 serine
residues. These findings would argue
that the in vivo proteolytic
processing of the cathepsin D single
chain is probably not carried out by a
specific "processing
protease." Model building of the
cathepsin D processing region
conformation was conducted utilizing
the homology between procathepsin D
and porcine pepsinogen. The
beta-hairpin structure of the
processing region was found to (i)
interact with the activation peptide
of the procathepsin D in a
beta-structure and (ii) place the Cys
residue in the processing region
within disulfide linkage distance to
Cys-27 of cathepsin D light chain.
These observations support the view
that the processing region of
cathepsin D may function to stabilize
the conformation of procathepsin D and
may play a role in its activation.
- Language of Publication
- English
- Unique Identifier
- 89034127
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- MeSH Heading (Major)
- Cathepsin D|*GE; Protein Processing,
Post-Translational|*
- MeSH Heading
- Amino Acid Sequence; Animal; Base
Sequence; Cattle; Comparative Study;
Computer Graphics; Human; Models,
Molecular; Molecular Sequence Data;
Protein Conformation; Rats; Species
Specificity; Support, U.S. Gov't,
P.H.S.; Swine
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9258
- Country of Publication
- UNITED STATES
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- Title
- Granulocyte-angiotensin system.
Identification of angiotensinogen as
the plasma protein substrate of
leukocyte cathepsin G.
- Author
- Wintroub BU; Klickstein LB; Dzau VJ;
Watt KW
- Address
-
- Source
- Biochemistry, 1984 Jan, 23:2, 227-32
- Abstract
- Cathepsin G, a human lysosomal
neutral protease, converts angiotensin
I to angiotensin II and cleaves
angiotensin II from a plasma protein
substrate. Experiments were designed
that identified and characterized
cathepsin G substrate as human
angiotensinogen. A total of 2, 5, and
10 micrograms of purified substrate,
incubated with 2 microL of partially
purified human renin (2 Goldblatt
units/mg) for 60 min at 37 degrees C,
generated 2, 9, and 22 pmol of
angiotensin I. Cathepsin G substrate
and renin substrate activities
copurified during Affi-Gel Blue
affinity chromatography,
hydroxylapatite chromatography,
phenyl-Sepharose chromatography, and
S-200 gel filtration. Disc gel
electrophoresis of 10 micrograms of
purified protein gave a single band
containing both activities. The
amino-terminal sequence contained the
covalent structure of angiotensin I
and was
Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-X-Glu-Ser-Thr-Cys-Gl
u-. Reduced and unreduced
angiotensinogens were subjected to
sodium dodecyl sulfate gel
electrophoresis, and each gel showed
two bands of Mr 65 000 and 62 000. The
isoelectric point of the Mr 65 000
form was pH 4.5-4.3 and the Mr 62 000
form was pH 4.9. Functional,
structural, and physiochemical
evidence demonstrates that the
substrate of cathepsin G is
angiotensinogen. Thus, human
neutrophils may utilize angiotensin I
or angiotensinogen as substrate for
angiotensin II generation. The
granulocyte-angiotensin system does
not require renin or converting enzyme
and may function as a mobile effector
pathway which modulates tissue blood
flow and/or vascular permeability.
- Language of Publication
- English
- Unique Identifier
- 84128540
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- MeSH Heading (Major)
- Angiotensinogen|IP/*ME; Angiotensins|*ME;
Cathepsins|*BL/IP; Granulocytes|*EN;
Leukocytes|*EN
- MeSH Heading
- Amino Acids|AN; Human; Kinetics;
Lysosomes|EN; Renin-Angiotensin
System; Substrate Specificity;
Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-2960
- Country of Publication
- UNITED STATES
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- Title
- Modulation of interferon gamma
induced increases in cathepsin B in
THP-1 cells by adrenergic agonists and
antagonists.
- Author
- Li Q; Bever CT Jr
- Address
- Departments of Neurology and
Pharmacology and Experimental
Therapeutics, Baltimore Veterans
Affairs Medical Center, Baltimore,
Maryland, 21201, USA.
- Source
- Cell Biol Int, 1998, 22:1, 13-20
- Abstract
- In order to investigate the possible
modulation of macrophage function by
the autonomic nervous system, the
effect of adrenergic agonists and
antagonists on interferon (IFN)-gamma-induced
increases in cathepsin B (CB) in a
macrophage-like cell line was studied.
It has been shown previously that IFN-gamma
induces increased CB activity in
phorbol myristate acetate (PMA)-primed
THP-1 cells. Isoproterenol (ISO) (10
micrometers), a mixed beta-receptor
agonist, increased the induction of CB
activity in the cells but
norepinephrine (10 micrometers) and
epinephrine (10 micrometers), the
alpha and beta receptor agonists, had
little effect. The addition of the
mixed alpha-receptor antagonist
phentolamine (10 micrometers) had no
effect on ISO induced increases but
the mixed beta-receptor antagonist
propranolol (10 micrometers) and the
selective beta1-receptor antagonist
atenolol produced significant
inhibition. These results suggest that
the activation of beta-receptors could
be involved in the induction of CB
activity in macrophages and provide a
possible mechanism for the regulation
of macrophage effector function by the
autonomic nervous system. Dibutyryl
cAMP (1 mm) alone also induced
increases in CB in THP-1 cells, and
H-89 or HA1004 abrogated the effect of
dibutyryl cAMP, suggesting that the
effect of ISO on CB could be through
the elevation of cAMP and the
activation of cAMP-dependent protein
kinases. Copyright 1998 Academic
Press.
- Language of Publication
- English
- Unique Identifier
- 99047439
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- MeSH Heading (Major)
- Adrenergic Agonists|*PD; Adrenergic
Antagonists|*PD; Cathepsin B|*ME;
Interferon-gamma, Recombinant|*PD
- MeSH Heading
- Bucladesine|PD; Cell Line; Cyclic
AMP-Dependent Protein Kinases|ME;
Human; Isoproterenol|PD;
Macrophages|DE/EN; Support, Non-U.S.
Gov't; Support, U.S. Gov't,
Non-P.H.S.; Tetradecanoylphorbol
Acetate|PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 1065-6995
- Country of Publication
- ENGLAND
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- Title
- Ontogeny, immunocytochemical
localization, and biochemical
properties of the pregnancy-associated
uterine elastase/cathepsin-G protease
inhibitor, antileukoproteinase (ALP):
monospecific antibodies to a synthetic
peptide recognize native ALP.
- Author
- Simmen RC; Michel FJ; Fliss AE;
Smith LC; Fliss MF
- Address
- Department of Animal Science,
University of Florida, Gainesville
32611.
- Source
- Endocrinology, 1992 Apr, 130:4,
1957-65
- Abstract
- Expression of the mRNA encoding the
elastase/cathepsin-G protease
inhibitor, antileukoproteinase (ALP),
is highest in pig uterus during mid-
and late pregnancy, suggesting a stage
of pregnancy-dependent role for ALP in
feto-maternal interactions. To
elucidate a function for ALP in these
events, immunogenic probes were
developed to localize sites of ALP
expression in the environment of the
developing fetus. Monospecific
antibodies raised against a 16-mer
synthetic peptide corresponding to
residues 21-36 (ALP 16P) of the
deduced amino acid sequence of pig
uterine ALP were generated by active
immunization of sheep. ALP 16P
conjugated to keyhole limpet
hemocyanin elicited high titer
antibodies that were specific to ALP.
The antipeptide antibodies were used
to characterize pig uterine ALP from
allantoic fluids. Uterine ALP has an
approximate mol wt of 14,000 and a pI
of 8.2 and exhibits elastase inhibitor
activity. Amino-terminal amino acid
sequencing of uterine ALP indicated
the sequence AENALKGGACPPRKIVQC, which
has 44% identity with the
corresponding region in human
bronchial ALP. RIA for ALP, developed
using ALP 16P as standard and
iodinated tracer, demonstrated the
presence of immunoreactive ALP in
early, mid-, and late pregnant
endometrium and myometrium, placenta,
allantoic fluids, fetal cord blood,
and fetal liver. ALP was undetectable
in the maternal circulation. The ALP
levels in endometrium, allantoic
fluids, and fetal cord blood changed
with the stage of pregnancy; however,
ALP content in placenta, myometrium,
and fetal liver, although different
among tissues, remained invariant
during gestation. By
immunocytochemical analyses, ALP was
localized in the glandular epithelium
of the uterus, in placenta, and in
fetal liver, consistent with the
presence of immunoreactive ALP as
measured by RIA. The localization of
uterine ALP in placenta and its
corresponding transport to fetal
circulation provide strong evidence to
support a physiological function for
the protease inhibitor in the
biological mechanisms controlling
fetal development in utero.
- Language of Publication
- English
- Unique Identifier
- 92191891
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- MeSH Heading (Major)
- Antibodies|*IM; Serine Proteinase
Inhibitors|*AN/GE/IM
- MeSH Heading
- Amino Acid Sequence; Animal; Female;
Immunohistochemistry; Maternal-Fetal
Exchange; Molecular Sequence Data;
Pregnancy; RNA, Messenger|AN; Sheep;
Support, U.S. Gov't, Non-P.H.S.;
Support, U.S. Gov't, P.H.S.; Swine;
Uterus|CH
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0013-7227
- Country of Publication
- UNITED STATES
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- Title
- Histochemical localization of
cathepsin B at the invasion front of
the rabbit V2 carcinoma.
- Author
- Graf M; Baici A; Sträuli P
- Address
-
- Source
- Lab Invest, 1981 Dec, 45:6, 587-96
- Abstract
- To clarify the role of cathepsin B
in tumor invasion, the enzyme was
visualized in tissue frozen sections
of the subcutaneously growing rabbit
V2 carcinoma. Localization of
cathepsin B was achieved by
immunofluorescent staining and by
enzyme histochemistry. For the former
approach, a sheep antiserum was raised
against purified cathepsin B from
rabbit liver. The antibodies, isolated
by immunoadsorption, reacted
monospecifically with rabbit liver
cathepsin B in Ouchterlony double
diffusion and in immunoelectrophoresis.
In the enzyme histochemical assay,
Z-Ala-Arg-Arg-methoxynaphtylamide was
used as fluorogenic substrate and
nitrosalicylaldehyde as coupling
agent. With both methods, cathepsin B
was found to be localized within
fibroblasts and leukocytes assembled
at the tumor invasion front. In
addition, immunofluorescent staining
demonstrated the occurrence of the
enzyme in the extracellular matrix
surrounding tumor cell clusters.
Carcinoma cells always remained
unstained. The conclusion is drawn
that cathepsin B is chiefly produced
by host cells which are stimulated to
increase synthesis and to release the
enzyme under the influence of the
tumor. A dual function can be ascribed
to cathepsin B concentrated in the
vicinity of the tumor: it operates
intracellularly (in host cells)
through degradation of endocytosed
protein and extracellularly through
activation of collagenase. The
resulting lytic action on host
structures appears to be a
prerequisite for local spread of the
V2 carcinoma.
- Language of Publication
- English
- Unique Identifier
- 82102255
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- MeSH Heading (Major)
- Cathepsins|IM/*IP; Cell
Transformation, Neoplastic|*AN/PA;
Liver|*AN; Neoplasms,
Experimental|*AN/PA
- MeSH Heading
- Animal; Antibodies; Fluorescent
Antibody Technique; Histocytochemistry;
Rabbits; Sheep; Support, Non-U.S.
Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0023-6837
- Country of Publication
- UNITED STATES
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- Title
- Direct affinity purification and
supramolecular organization of human
lysosomal cathepsin A.
- Author
- Pshezhetsky AV; Potier M
- Address
- Service de GÆenÆetique MÆedicale,
HÈopital Sainte-Justine, MontrÆeal,
QuÆebec, Canada.
- Source
- Arch Biochem Biophys, 1994 Aug,
313:1, 64-70
- Abstract
- Cathepsin A (also named
"protective protein" and
carboxypeptidase L) stabilizes beta-galactosidase
and activates neuraminidase by forming
with them a high-molecular-weight
lysosomal complex. We determined the
main forms of the supramolecular
organization of human placental
cathepsin A and the quantitative
relationship between them, using an
affinity chromatography on
agarose-Phe-Leu for direct
purification of cathepsin A. We found
that cathepsin A in human placenta
exists as the following three forms: a
1270-kDa complex with beta-galactosidase
and neuraminidase (about 1% of total
cathepsin A), a 680-kDa complex with
beta-galactosidase (30-40% of total),
and a free 98-kDa cathepsin A dimer
(60-70% of total). All forms are in
dynamic equilibrium with each other,
but almost all placental beta-galactosidase
is associated with cathepsin A in the
680-kDa complex. The main properties
of free cathepsin A (including the
capacity to associate with beta-galactosidase)
were found to be identical to those of
cathepsin A obtained by dissociation
of the 680-kDa complex. The presence
of a free cathepsin A pool in the
lysosome is connected with its sixfold
overproduction in the cell compared to
beta-galactosidase and may be
necessary to ensure cathepsin A
proteolytic function in addition to
its protective role for beta-galactosidase
and neuraminidase in the lysosomal
multienzymatic complex. Such a dual
function of cathepsin A is also
confirmed by our finding that it is
the only carboxypeptidase of placenta
extract able to catalyze the
hydrolysis of both carbobenzoxy (CBZ)-Glu-Tyr
and CBZ-Phe-Leu dipeptide substrates.
- Language of Publication
- English
- Unique Identifier
- 94330723
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- MeSH Heading (Major)
- Carboxypeptidases|*CH; Cathepsins|*CH;
Lysosomes|EN/*UL
- MeSH Heading
- beta-Galactosidase|CH; Amino Acid
Sequence; Human; Macromolecular
Systems; Molecular Sequence Data;
Neuraminidase|CH; Placenta|EN/UL;
Protein Binding
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0003-9861
- Country of Publication
- UNITED STATES
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- Title
- Morphine induces splenocyte
apoptosis and enhanced mRNA expression
of cathepsin-B.
- Author
- Singhal PC; Reddy K; Franki N;
Sanwal V; Gibbons N
- Address
- Department of Medicine, Long Island
Jewish Medical Center, New Hyde Park,
New York 11040, USA.
- Source
- Inflammation, 1997 Dec, 21:6, 609-17
- Abstract
- Morphine has been demonstrated to
modulate immune function. We studied
whether morphine modulates apoptosis
of splenocytes. Splenocytes were
isolated from control and morphine
treated rats. Splenocytes isolated
from morphine treated rats showed
increased percentage (P < 0.001) of
apoptosis when compared to splenocytes
isolated from untreated rats (control,
4.7 +/- 1.0% apoptotic splenocytes/field
vs. morphine, 47.8 +/- 3.4% apoptotic
splenocytes/field). These results were
further confirmed by gel
electrophoresis as well as by
end-labeling DNA of splenocytes
isolated from control and morphine
treated rats. Splenocytes from
morphine treated rats showed a
classical ladder pattern with integer
multiples of 180 base pairs.
Splenocytes from morphine treated rats
also showed increased mRNA expression
of cathepsin-B, a gene associated with
active cell death. These results
suggest that morphine may also be
modulating immune function by
enhancing apoptosis of splenocytes.
- Language of Publication
- English
- Unique Identifier
- 98091743
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- MeSH Heading (Major)
- Apoptosis|*DE; Cathepsin B|*BI;
Morphine|*PD; Narcotics|*PD; Spleen|ME/*PA
- MeSH Heading
- Animal; Rats; Rats, Sprague-Dawley;
RNA, Messenger|BI; Support, U.S.
Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0360-3997
- Country of Publication
- UNITED STATES
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- Title
- The human cathepsin F gene--a fusion
product between an ancestral cathepsin
and cystatin gene.
- Author
- Wex T; Wex H; Brömme D
- Address
- Department of Human Genetics, Mount
Sinai School of Medicine, New York, NY
10029, USA.
- Source
- Biol Chem, 1999 Dec, 380:12, 1439-42
- Abstract
- Human cathepsin F is a novel papain-like
cysteine protease of unknown function.
Here, we describe the complete human
cathepsin F (CTSF) gene which is
composed of 13 exons. In addition to a
previous report, two novel upstream
located exons whose splice sites
interrupted the propeptide of
cathepsin F within the 'cystatin-like'
domain, recently described by Nagler
et al. (Biochem. Biophys. Res. Comm.
257, 313-318, 1999) were identified. A
comparison of the genomic structures
between this novel part of the
cathepsin F gene and those of several
cystatin genes revealed striking
similarities, supporting the
hypothesis that the cathepsin F gene
resulted from a gene fusion between an
ancestral cystatin and cathepsin gene.
- Language of Publication
- English
- Unique Identifier
- 20125514
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- MeSH Heading (Major)
- Cathepsins|*GE; Cystatins|*GE
- MeSH Heading
- Amino Acid Sequence; Exons; Human;
Introns; Molecular Sequence Data;
Recombinant Fusion Proteins|GE;
Support, Non-U.S. Gov't; Support, U.S.
Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 1431-6730
- Country of Publication
- GERMANY
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- Title
- Adsorption and helical coiling of
amphipathic peptides on lipid vesicles
leads to negligible protection from
cathepsin B or cathepsin D.
- Author
- Goldschmidt TG; Reyes VE; You G;
Nelson DJ; Reisert PS; Anderson J;
Mole J; Humphreys RE
- Address
- Department of Pharmacology,
University of Massachusetts Medical
School, Worcester 01655.
- Source
- Immunol Invest, 1993 Feb, 22:1,
25-40
- Abstract
- The processing of antigenic peptides
for presentation by MHC molecules to T
cells, may depend upon the function of
a second, consensus sequence in or
near the T cell-presented epitope. One
such processing-regulating sequence
appears to be composed of amino acids
Leu, Ile, Val, Phe, and Met recurring
in a fashion to form a longitudinal,
hydrophobic strip when the excised
peptide is coiled as an alpha-helix.
Such a hydrophobic strip-of-helix may:
(a) scavenge peptides from lumens onto
lipid membranes of digestion vesicles,
(b) stabilize peptides there as
protease-resistant helices, (c)
specify recognition by the antigenic
peptide-binding sites of chaperonin
proteins, transmembranal transporters,
or MHC molecules. By circular
dichroism and electron paramagnetic
resonance, we demonstrated that
peptides with recurrent hydrophobic
residues potentially forming
longitudinal strips adsorbed to, and
partially coiled as helices on,
di-O-hexadecyl, D-L-alpha-phosphatidylcholine
(DHPC) vesicles. Cathepsin B or
cathepsin D cleavages of three such
peptides were identified. With either
enzyme, it made no significant
difference whether a peptide substrate
was in solution or bound to vesicles
in terms of efficiency and specificity
of peptide bond cleavages. We conclude
that protease resistance, per se, of
membrane-adsorbed, helically coiled
peptides is not a major factor in the
selection for T cell presentation of
epitopes in peptides which have a
motif with a longitudinal hydrophobic
strip.
- Language of Publication
- English
- Unique Identifier
- 93179049
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- MeSH Heading (Major)
- Cathepsin B|*ME; Cathepsin D|*ME;
Liposomes|*; Peptide Fragments|*CH/DE;
Protein Structure, Secondary|*
- MeSH Heading
- Adsorption; Amino Acid Sequence;
Animal; Antigen-Presenting Cells|ME;
Electron Spin Resonance Spectroscopy;
Molecular Sequence Data; Phospholipid
Ethers; Substrate Specificity;
Support, Non-U.S. Gov't; Support, U.S.
Gov't, Non-P.H.S.; Support, U.S.
Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0882-0139
- Country of Publication
- UNITED STATES
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- Title
- Crystal structure of porcine
cathepsin H determined at 2.1 A
resolution: location of the mini-chain
C-terminal carboxyl group defines
cathepsin H aminopeptidase function.
- Author
- Guncar G; Podobnik M; Pungercar J;
Strukelj B; Turk V; Turk D
- Address
- Department of Biochemistry and
Molecular Biology, JoÅzef Stefan
Institute, Ljubljana, Slovenia.
gregor.guncar@ijs.si
- Source
- Structure, 1998 Jan, 6:1, 51-61
- Abstract
- BACKGROUND: Cathepsin H is a
lysosomal cysteine protease, involved
in intracellular protein degradation.
It is the only known mono-aminopeptidase
in the papain-like family and is
reported to be involved in tumor
metastasis. The cathepsin H structure
was determined in order to investigate
the structural basis for its
aminopeptidase activity and thus to
provide the basis for structure-based
design of synthetic inhibitors.
RESULTS: The crystal structure of
native porcine cathepsin H was
determined at 2.1 A resolution. The
structure has the typical papain-family
fold. The so-called mini-chain, the
octapeptide EPQNCSAT, is attached via
a disulfide bond to the body of the
enzyme and bound in a narrowed
active-site cleft, in the
substrate-binding direction. The
mini-chain fills the region that in
related enzymes comprises the
non-primed substrate-binding sites
from S2 backwards. CONCLUSIONS: The
crystal structure of cathepsin H
reveals that the mini-chain has a
definitive role in substrate
recognition and that carbohydrate
residues attached to the body of the
enzyme are involved in positioning the
mini-chain in the active-site cleft.
Modeling of a substrate into the
active-site cleft suggests that the
negatively charged carboxyl group of
the C terminus of the mini-chain acts
as an anchor for the positively
charged N-terminal amino group of a
substrate. The observed displacements
of the residues within the active-site
cleft from their equivalent positions
in the papain-like endopeptidases
suggest that they form the structural
basis for the positioning of both the
mini-chain and the substrate,
resulting in exopeptidase activity.
- Language of Publication
- English
- Unique Identifier
- 98154318
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- MeSH Heading (Major)
- Aminopeptidases|*CH; Cathepsins|*CH;
Cysteine Endopeptidases|*CH
- MeSH Heading
- Amino Acid Sequence; Animal; Binding
Sites|PH; Cathepsin B|CH;
Crystallography, X-Ray; Cysteine
Proteinase Inhibitors|ME;
Glycosylation; Lysosomes|EN; Models,
Molecular; Molecular Sequence Data;
Oligosaccharides|CH; Protein
Precursors|CH; Protein Processing,
Post-Translational|PH; Protein
Structure, Secondary; Sequence
Alignment; Support, Non-U.S. Gov't;
Swine
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0969-2126
- Country of Publication
- ENGLAND
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- Title
- Characterization of recombinant rat
cathepsin B and nonglycosylated
mutants expressed in yeast. New
insights into the pH dependence of
cathepsin B-catalyzed hydrolyses.
- Author
- Hasnain S; Hirama T; Tam A; Mort JS
- Address
- Protein Structure and Design
Section, National Research Council of
Canada, Ottawa, Ontario.
- Source
- J Biol Chem, 1992 Mar, 267:7,
4713-21
- Abstract
- The cysteine proteinase rat
cathepsin B was expressed in yeast in
an active form and was found to be
heterogeneously glycosylated at the
consensus sequence for N-linked
oligosaccharide substitution. Purified
enzyme fractions containing the
highest levels of glycosylation were
shown to have reduced activity. A
glycosylation minus mutant constructed
by site-directed mutagenesis (by
changing the Ser to Ala in the
consensus sequence) was still secreted
by the yeast and was shown to be
functionally identical with purified
rat liver cathepsin B. Recombinant
cathepsin B was used to further
characterize the pH dependence of
cathepsin B-catalyzed hydrolyses using
7-amido-4-methylcoumarin (AMC) and p-nitroaniline
(pNA) substrates with arginine as the
P1, and either arginine or
phenylalanine as the P2 residue. The
AMC and pNA groups give insights into
the leaving group binding site (P') of
cathepsin B. These studies show for
the first time that at least seven
dissociable groups are involved in
substrate binding and hydrolysis in
cathepsin B activity. Two of these
groups, with pKa values of 6.9 and 7.7
in the recombinant enzyme, are in the
leaving group binding site and are
most likely His110 and His111. The
same groups in rat liver cathepsin B
have higher pKa values than in
recombinant cathepsin B, but have
identical function in the two enzymes.
Two other groups are probably the
active site Cys29 and His199 with pKa
values of 3.6 and 8.6, respectively. A
group with a pKa of 5.1 interacts with
substrates containing Arg at P2, and
the group is most likely Glu245. The
remaining two groups, one with a pKa
of about 4.9 and the other about 5.3,
are most likely carboxyl residues
possibly interacting with Arg at P1 in
the substrate. The possible candidates
on the basis of the x-ray structure
are Asp22, Asp69, Glu171, and Glu122,
all found within a 13 A radius from
the active site thiol of Cys29.
- Language of Publication
- English
- Unique Identifier
- 92165832
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- MeSH Heading (Major)
- Cathepsin B|*GE/ME; Mutation|*;
Saccharomyces cerevisiae|*EN
- MeSH Heading
- Animal; Catalysis; Cloning,
Molecular; Electrophoresis,
Polyacrylamide Gel; Gene Expression;
Glycosylation; Hydrogen-Ion
Concentration; Hydrolysis; Kinetics;
Liver|EN; Rats; Recombinant
Proteins|GE/ME; Substrate Specificity;
Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9258
- Country of Publication
- UNITED STATES
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- Title
- Adsorption and helical coiling of
amphipathic peptides on lipid vesicles
leads to negligible protection from
cathepsin B or cathepsin D.
- Author
- Goldschmidt TG; Reyes VE; You G;
Nelson DJ; Reisert PS; Anderson J;
Mole J; Humphreys RE
- Address
- Department of Pharmacology,
University of Massachusetts Medical
School, Worcester 01655.
- Source
- Immunol Invest, 1993 Feb, 22:1,
25-40
- Abstract
- The processing of antigenic peptides
for presentation by MHC molecules to T
cells, may depend upon the function of
a second, consensus sequence in or
near the T cell-presented epitope. One
such processing-regulating sequence
appears to be composed of amino acids
Leu, Ile, Val, Phe, and Met recurring
in a fashion to form a longitudinal,
hydrophobic strip when the excised
peptide is coiled as an alpha-helix.
Such a hydrophobic strip-of-helix may:
(a) scavenge peptides from lumens onto
lipid membranes of digestion vesicles,
(b) stabilize peptides there as
protease-resistant helices, (c)
specify recognition by the antigenic
peptide-binding sites of chaperonin
proteins, transmembranal transporters,
or MHC molecules. By circular
dichroism and electron paramagnetic
resonance, we demonstrated that
peptides with recurrent hydrophobic
residues potentially forming
longitudinal strips adsorbed to, and
partially coiled as helices on,
di-O-hexadecyl, D-L-alpha-phosphatidylcholine
(DHPC) vesicles. Cathepsin B or
cathepsin D cleavages of three such
peptides were identified. With either
enzyme, it made no significant
difference whether a peptide substrate
was in solution or bound to vesicles
in terms of efficiency and specificity
of peptide bond cleavages. We conclude
that protease resistance, per se, of
membrane-adsorbed, helically coiled
peptides is not a major factor in the
selection for T cell presentation of
epitopes in peptides which have a
motif with a longitudinal hydrophobic
strip.
- Language of Publication
- English
- Unique Identifier
- 93179049
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- MeSH Heading (Major)
- Cathepsin B|*ME; Cathepsin D|*ME;
Liposomes|*; Peptide Fragments|*CH/DE;
Protein Structure, Secondary|*
- MeSH Heading
- Adsorption; Amino Acid Sequence;
Animal; Antigen-Presenting Cells|ME;
Electron Spin Resonance Spectroscopy;
Molecular Sequence Data; Phospholipid
Ethers; Substrate Specificity;
Support, Non-U.S. Gov't; Support, U.S.
Gov't, Non-P.H.S.; Support, U.S.
Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0882-0139
- Country of Publication
- UNITED STATES
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- Title
- Dissection of laminin by cathepsin G
into its long-arm and short-arm
structures and localization of regions
involved in calcium dependent
stabilization and self-association.
- Author
- Bruch M; Landwehr R; Engel J
- Address
- Abteilung Biophysikalische Chemie,
Biozentrum der UniversitÂat, Basel,
Switzerland.
- Source
- Eur J Biochem, 1989 Nov, 185:2,
271-9
- Abstract
- Native laminin-nidogen complex
isolated from mouse Engelbreth-Holm-Swarm
tumor was treated with purified
cathepsin G or leucocyte elastase, two
neutral serine proteases which play a
role in inflammatory processes
accompanied by degradation of basement
membranes. Both enzymes were found to
be more active than porcine pancreatic
elastase. In the absence of Ca2+,
laminin fragments produced by
leucocyte elastase resembled those
formed by the pancreatic enzyme but at
physiological concentrations of Ca2+
cleavage by cathepsin G was much more
selective. Initially laminin (900 kDa)
was cleaved at two major sites only
with similar rates leading to three
fragments. Fragment C1-4 (about 550
kDa) comprises the intact three short
arms of the molecule and fragment C8-9
(about 350 kDa) contains the entire
triple-coiled region by which its
three chains are assembled and the
major part of the terminal globular
domain of the long arm. The remaining
C-terminal region of this domain was
recovered as fragment C3 of about 50
kDa. Stabilization against proteolytic
attack was restricted to the region of
fragment C1-4 and only this fragment
exhibited strong Ca2+ dependent
self-association similar to that of
intact laminin or of its complex with
nidogen. The associative properties of
fragment C1-4 were dramatically
diminished upon removal of the tip of
one of the short arms comprising
fragment 4. In addition, this provides
a clear assignment of the important
laminin function to a distinct domain
in one of its short arms. The new
fragment C8-9 may be employed for
exploring the properties and possible
functions of the upper long-arm region
which so far has not been available as
a fragment.
- Language of Publication
- English
- Unique Identifier
- 90060110
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- MeSH Heading (Major)
- Calcium|*ME; Cathepsins|*PD; Laminin|*ME/UL
- MeSH Heading
- Animal; Human; Membrane Proteins|ME;
Mice; Molecular Weight; Pancreatic
Elastase|PD; Peptide Fragments|ME;
Protein Conformation; Support,
Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0014-2956
- Country of Publication
- GERMANY, WEST
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- Title
- Human leukocyte cathepsin G and
elastase specifically suppress
thrombin-induced prostacyclin
production in human endothelial cells.
- Author
- Weksler BB; Jaffe EA; Brower MS;
Cole OF
- Address
- Department of Medicine, Cornell
University Medical College, New York,
NY.
- Source
- Blood, 1989 Oct, 74:5, 1627-34
- Abstract
- Polymorphonuclear leukocytes (PMN)
when activated release products that
can potentially injure endothelial
cells or alter endothelial function.
Exposure of cultured human umbilical
vein endothelial cells to cathepsin G
and elastase isolated from human PMN
at concentrations reached in vivo (100
ng/mL to 10 micrograms/mL) selectively
inhibited thrombin-induced
prostacyclin production and the
thrombin-induced rise in cytosolic
free calcium ([Ca++]i) concentration.
These proteases also blocked
thrombin-induced release of
arachidonic acid from prelabeled
endothelial cells (EC). In contrast,
induction of prostacyclin (PGI2)
production by arachidonate, histamine,
or the calcium ionophore A23187 was
not altered by treatment of EC with
these proteases. The effects of the
proteases were
concentration-dependent, were blocked
by serum or serum protease inhibitors,
and were reversed when the endothelial
cells were further cultured for 24
hours in the absence of the proteases.
Elastase, but not cathepsin G, also
produced detachment of endothelial
cells. Thus, the major leukocyte
proteases selectively suppress
thrombin-induced prostacyclin
production by human vascular
endothelial cells and may alter the
hemostatic balance at sites of PMN
activation.
- Language of Publication
- English
- Unique Identifier
- 90001545
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- MeSH Heading (Major)
- Cathepsins|*BL/IP; Endothelium,
Vascular|DE/*ME; Epoprostenol|*BI;
Leukocytes|*EN; Pancreatic
Elastase|*BL/IP; Thrombin|*PH
- MeSH Heading
- alpha 1-Antitrypsin|PH; alpha-Macroglobulins|PH;
Arachidonic Acids|ME; Calcimycin|PD;
Calcium|ME; Cells, Cultured; Human;
Kinetics; Neutrophils|EN; Support,
U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-4971
- Country of Publication
- UNITED STATES
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- Title
- Neutrophil elastase and cathepsin G:
structure, function, and biological
control.
- Author
- Watorek W; Farley D; Salvesen G;
Travis J
- Address
- Department of Biochemistry,
University of Georgia, Athens 30602.
- Source
- Adv Exp Med Biol, 1988, 240:, 23-31
- Abstract
- When neutrophils invade inflamed
areas of the body to remove either
dead or foreign components they
inadvertently release potent enzymes
which can, if not properly controlled,
cause severe damage to healthy tissue.
This can lead to a myriad of diseases
including emphysema, rheumatoid
arthritis, and glomuerlopnephritis,
all of which are really problems of
abnormal connective tissue turnover
due to uncontrolled protelysis by
neutrophil elastase and cathepsin G.
An important step in elucidating the
functions of both elastase and
cathepsin G has been made by virtue of
the fact that the amino acid sequence
of each has been determined.
Furthermore, the crystal structure of
one, neutrophil elastase, is now
understood. With this knowledge in
mind and with the potential for a
similar understanding of the mechanism
of action of cathepsin G, it should
soon be possible to produce synthetic
inhibitors of each enzyme which can
act as adjunct inhibitors to those
naturally circulating in the blood or
present in other tissues. As a result
there is great hope for reducing the
severity of injury produced by these
enzymes and, therefore, in decreasing
the risk for development of the
debilitating diseases associated with
abnormal proteolysis by neutrophil
proteinases.
- Language of Publication
- English
- Unique Identifier
- 89225435
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- MeSH Heading (Major)
- Cathepsins|*PH; Neutrophils|*EN;
Pancreatic Elastase|*PH
- MeSH Heading
- Amino Acid Sequence; Blood Proteins;
Carbohydrates|AN; Human; Molecular
Sequence Data; Serine
Endopeptidases|ME; Structure-Activity
Relationship; Substrate Specificity;
Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0065-2598
- Country of Publication
- UNITED STATES
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- Title
- Cathepsin D inactivates cysteine
proteinase inhibitors, cystatins.
- Author
- Lenarcic B; Kos J; Dolenc I;
Lucovnik P; Krizaj I; Turk V
- Address
- Department of Biochemistry, J.
Stefan Institute, Ljubljana,
Yugoslavia.
- Source
- Biochem Biophys Res Commun, 1988
Jul, 154:2, 765-72
- Abstract
- The formation of inactive complexes
in excess molar amounts of human
cathepsins H and L with their protein
inhibitors human stefin A, human
stefin B and chicken cystatin at pH
5.6 has been shown by measurement of
enzyme activity coupled with
reverse-phase HPLC not to involve
covalent cleavage of the inhibitors.
Inhibition must be the direct result
of binding. On the contrary the
interaction of cystatins with aspartic
proteinase cathepsin D at pH 3.5 for
60 min followed by HPLC resulted in
their inactivation accompanied by
peptide bond cleavage at several
sites, preferentially those involving
hydrophobic amino acid residues. The
released peptides do not inhibit
papain and cathepsin L. These results
explain reported elevated levels of
cysteine proteinases and lead to the
proposal that cathepsin D exerts an
important function, through
inactivation of cystatins, in the
increased activities of cysteine
proteinases in human diseases
including muscular distrophy.
- Language of Publication
- English
- Unique Identifier
- 88293513
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- MeSH Heading (Major)
- Cathepsin D|*ME; Cysteine
Endopeptidases|*AI; Protease
Inhibitors|*; Proteins|*AI
- MeSH Heading
- Amino Acid Sequence; Chromatography,
High Pressure Liquid; Human; Molecular
Sequence Data; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-291X
- Country of Publication
- UNITED STATES
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- Title
- Cathepsin B and L in isolated
proximal tubular segments during acute
and chronic proteinuria.
- Author
- Eisenberger U; Fels LM; Olbricht CJ;
Stolte H
- Address
- Department of Internal Medicine,
Hannover Medical School, Germany.
- Source
- Ren Physiol Biochem, 1995 Mar, 18:2,
89-96
- Abstract
- Acute and chronic proteinuria were
studied in rats, using lysosomal
cathepsin B and L as marker enzymes
for tubular protein degradation. The
activity of cathepsin B and L has been
determined in microdissected segments
S1, S2 and S3 of the proximal tubule
by an ultramicroassay.
Z-Phenylalanyl-arginine-7-amido-4-methylcoumarin
served as a substrate. In
normoproteinuric Sprague-Dawley rats,
induction of acute unselective
glomerular proteinuria with Adriamycin
(5 mg/kg body weight) revealed a
moderate activity increase of
cathepsin B and L in the S2 segment,
reaching 12.6 +/- 5.6 versus 8.6 +/-
4.2 pmol.mm-1.min-1 in controls. In
contrast, Munich Wistar Frömter (MWF)
rats, that are characterized by a
genetically determined, chronically
elevated glomerular protein excretion,
showed a very high activity of
cathepsin selectively in S2 of 25.0
+/- 12.1 pmol.mm-1.min-1. Acute
proteinuria induced by Adriamycin in
chronic proteinuric MWF rats could
increase cathepsin activity in the S3
segment only, showing 12.0 +/- 8.3
versus 6.8 +/- 4.0 pmol.mm-1.min-1 in
MWF control rats. In conclusion,
chronically increased protein
filtration changes the functional
reserve capacity of the proximal
tubule. While acutely induced
glomerular proteinuria in
normoproteinuric rats stimulates
lysosomal proteolytic activity mainly
in S2 segment, chronic proteinuric MWF
rats may display already a maximally
stimulated cathepsin activity in this
segment probably due to long-term
increased tubular protein load. In
case of acute elevation of chronic
proteinuria, the consecutive S3
segment shows increased lysosomal
function for protein conservation.
- Language of Publication
- English
- Unique Identifier
- 95288517
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- MeSH Heading (Major)
- Cathepsin B|*ME; Cathepsins|*ME;
Kidney Tubules, Proximal|*EN;
Proteinuria|CI/GE/*ME
- MeSH Heading
- Acute Disease; Animal; Chronic
Disease; Comparative Study;
Creatinine|UR; Doxorubicin; Female;
Nephrosis|CI/ME; Rats; Rats, Inbred WF;
Rats, Sprague-Dawley; Support,
Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 1011-6524
- Country of Publication
- SWITZERLAND
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- Title
- Regulation of cathepsin E expression
during human B cell differentiation in
vitro.
- Author
- Sealy L; Mota F; Rayment N; Tatnell
P; Kay J; Chain B
- Address
- Department of Immunology, UCL
Medical School, London, GB.
- Source
- Eur J Immunol, 1996 Aug, 26:8,
1838-43
- Abstract
- Cathepsin E is an aspartic
proteinase which has been implicated
in antigen processing in the class II
major histocompatibility complex
pathway. In this study we show that
cathepsin E, measured at both the
protein and message level, is
up-regulated late in human B cell
activation. The implications of this
observation in terms of cathepsin E
function are discussed.
- Language of Publication
- English
- Unique Identifier
- 96350506
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- MeSH Heading (Major)
- B-Lymphocytes|*IM/*ME; Cathepsins|*BI/GE
- MeSH Heading
- Adolescence; Adult; Base Sequence;
Cell Differentiation|GE/IM; Cell Line;
Child; Child, Preschool; Epitopes|IM;
Human; Infant; Lymphocyte
Transformation; Molecular Sequence
Data; RNA, Messenger|AN; T-Lymphocytes|IM;
Tonsil
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0014-2980
- Country of Publication
- GERMANY
Record 44 from database:
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- Title
- Expression, subcellular distribution
and plasma membrane binding of
cathepsin B and gelatinases in bone
metastatic tissue.
- Author
- Arkona C; Wiederanders B
- Address
- Institute of Biochemistry, Medical
Faculty,
Friedrich-Schiller-University, Jena,
Germany.
- Source
- Biol Chem, 1996 Nov, 377:11, 695-702
- Abstract
- The possible application of
proteinase inhibitors in the support
of anti-tumor chemotherapy requires
profound knowledge of the proteinases
involved in malignant processes.
Therefore, the occurrence of
cathepsins B, D, H, L and S and of
gelatinases, urokinase plasminogen
activator and stromelysins was studied
in biopsies of aggressive human bone
metastases, of low invading basal cell
carcinomas, and in normal placenta as
control, by activity measurements and
zymographic techniques. Cathepsin B
and L, as well as gelatinase B, were
shown to be overexpressed in bone
metastases, suggesting a function
during the metastatic process.
Subcellular fractionation allowed
detection of differential sorting of
cathepsin B and gelatinases in
metastatic tissue and also in normal
human placenta. Plasma membrane
binding could be demonstrated for both
cathepsin B and gelatinase B. Whereas
cathepsin B is at least partially
bound to plasma membranes via alpha
2-macroglobulin and its LRP/alpha
2-macroglobulin receptor, gelatinase B
binds to plasma membranes by an
unknown mechanism.
- Language of Publication
- English
- Unique Identifier
- 97119547
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- MeSH Heading (Major)
- Bone Neoplasms|EN/*SC; Cathepsin
B|*ME; Gelatinases|*ME
- MeSH Heading
- beta-N-Acetylhexosaminidase|ME; Acid
Phosphatase|ME; Cathepsins|ME; Cell
Membrane|EN; Collagenases|ME; Human;
Lactate Dehydrogenase|ME; Neoplasm
Metastasis; Phosphotransferases
(Alcohol Group Acceptor)|ME;
Subcellular Fractions|EN; Support,
Non-U.S. Gov't; Urokinase|ME;
5'-Nucleotidase|ME
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 1431-6730
- Country of Publication
- GERMANY
Record 45 from database:
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- Title
- Effects of in vitro cellular aging
on alkaline phosphatase, cathepsin
activities and collagen secretion of
human periodontal ligament derived
cells.
- Author
- Goseki T; Shimizu N; Iwasawa T;
Takiguchi H; Abiko Y
- Address
- Department of Orthodontics, Nihon
University School of Dentistry at
Matsudo, Chiba, Japan.
- Source
- Mech Ageing Dev, 1996 Nov, 91:3,
171-83
- Abstract
- It is believed that the degree of
periodontal tissue breakdown and tooth
loss increase with age. In periodontal
tissues which are gingiva, periodontal
ligament (PL), alveolar bone and tooth
cementum, the PL which is soft
connective tissue, lies between the
tooth cementum and alveolar bone,
having the primary function of tooth
support, and maintaining the
homeostasis of supporting tissues, as
well as providing the healing process.
We therefore investigated the effects
of in vitro cellular aging on alkaline
phosphatase (ALP), cathepsin
activities and collagen secretion from
human PL cells obtained from 18-23
year-old patients' teeth. ALP,
cathepsin activities and collagen
secretion may play important roles in
the remodeling and maintaining of
periodontal tissues. To investigate
the life span of PL cells, the cells
were sequentially subcultivated. The
maximum population doubling level of
the PL cells in the present experiment
was 22-25 passages. Investigating some
important biological activities of the
PL cells at different passage levels
(6-7, 30% of life span to 17-20, 75%
of life span), ALP activity and
collagen secretion were found to have
significantly decreased while
cathepsin B and L activities
significantly increased with cellular
aging. Since these biological
activities in human PL cells tend to
be more catabolic with increase in
cellular aging, the increase in
periodontal breakdown with age may be
partly related to the catabolic
changes of the PL cells themselves.
- Language of Publication
- English
- Unique Identifier
- 97208005
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- MeSH Heading (Major)
- Alkaline Phosphatase|*ME; Cathepsin
B|*ME; Cathepsins|*ME; Collagen|*SE;
Periodontal Ligament|CY/*ME
- MeSH Heading
- Adolescence; Adult; Cell Aging; Cell
Division; Female; Human; Support,
Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0047-6374
- Country of Publication
- IRELAND
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- Title
- Novel potential mechanism-based
inhibitors of human leukocyte elastase
and cathepsin G: derivatives of
isothiazolidin-3-one.
- Author
- Groutas WC; Chong LS; Venkataraman R
- Address
- Department of Chemistry, Wichita
State University, KS 67260.
- Source
- Biochem Biophys Res Commun, 1993
Dec, 197:2, 730-9
- Abstract
- A series of heterocyclic compounds
designed to function as
mechanism-based inhibitors of human
leukocyte elastase and cathepsin G has
been synthesized and their inhibitory
activity was investigated. These
isothiazolidin-3-one derivatives were
found to be effective inhibitors of
cathepsin G.
- Language of Publication
- English
- Unique Identifier
- 94092155
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- MeSH Heading (Major)
- Cathepsins|*AI/BL; Leukocytes|*EN;
Pancreatic Elastase|*AI; Protease
Inhibitors|CS/*PD; Thiazoles|CS/*PD
- MeSH Heading
- Comparative Study; Human; Kinetics;
Molecular Structure;
Structure-Activity Relationship;
Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-291X
- Country of Publication
- UNITED STATES
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- Title
- Lipid-rich residual bodies and
cathepsin D in the human uterus:
ultrastructural and quantitative
comparison between normal myometrium
and leiomyoma.
- Author
- Yamazaki K; Yakumaru K; Eyden BP
- Address
- Department of Pathology, Tokyo
Teishin Hospital, Japan.
- Source
- J Submicrosc Cytol Pathol, 1993 Jul,
25:3, 437-47
- Abstract
- The lipid-rich residual bodies (LRRB)
(Eyden et al., 1991) in human
myometrium and uterine leiomyoma
cells, have a distinctive
ultrastructure characterised by a rich
lipid content. To evaluate the
biological or pathological
significance in detail, normal
myometrium and uterine leiomyoma from
30 human cases were studied by
conventional histological,
histochemical, immunohistochemical and
electron microscopic methods. The
study included a quantitative analysis
of LRRBs of 3 premenarchic cases, 19
cases having a menstrual cycle, and 8
cases in menopause, in addition to 20
patients with histologically
conventional leiomyoma larger than 3
cm in diameter. The study revealed the
following findings: 1)
immunohistochemical distribution of
cathepsin D in the LRRB; 2)
histochemical demonstration of neutral
fat as the main content of LRRB; 3)
statistically significant decrease in
the distribution of LRRB in leiomyoma
tissue compared with normal myometrium;
4) an absence or minimal distribution
of LRRB in premenarchic myometrium; 5)
a moderately significant correlation
between the frequency of LRRB and
patient's age. The distribution of
cathepsin D within LRRB and the
differential expression of LRRBs in
the various smooth muscle cell tissues
of the uterus suggest a possible role
of ovarian hormones in the genesis of
LRRBs which may function in the intra-lysosomal
degradation of organelles produced
during hormonal cycling.
- Language of Publication
- English
- Unique Identifier
- 94006142
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- MeSH Heading (Major)
- Cathepsin D|*AN/ME; Inclusion
Bodies|*CH/UL; Leiomyoma|*CH/PA/UL;
Lipids|*AN/ME; Myometrium|*CH/CY/UL;
Uterine Neoplasms|*CH/PA/UL;
Uterus|*CH/CY/PA
- MeSH Heading
- Adolescence; Adult; Aged; Aged, 80
and over; Aging|ME/PH; Child;
Comparative Study; Female; Human;
Immunohistochemistry; Infant, Newborn;
Menopause|PH; Menstrual Cycle|PH;
Microscopy, Electron; Middle Age;
Organelles|UL
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 1122-9497
- Country of Publication
- ITALY
Record 48 from database:
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- Title
- Expression and partial
characterization of a cathepsin B-like
enzyme (Sm31) and a proposed 'haemoglobinase'
(Sm32) from Schistosoma mansoni.
- Author
- Götz B; Klinkert MQ
- Address
- Institute of Cell Biology, Consiglio
Nazionale delle Ricerche, Rome, Italy.
- Source
- Biochem J, 1993 Mar, 290 ( Pt 3):,
801-6
- Abstract
- Schistosoma mansoni protein Sm31 is
a cysteine proteinase similar to
mammalian lysosomal cathepsin B,
proposed to be a key enzyme in
schistosome metabolism. Protein Sm32
has been identified as a putative
cysteine proteinase termed a 'haemoglobinase'.
Since neither Sm31 nor Sm32 have been
completely purified, some controversy
of the nature of the 'true' digestive
enzyme still exists. By incubating a
radiolabelled cysteine-proteinase
active-site-directed synthetic
inhibitor with total S. mansoni
proteins, the target of inhibition was
Sm31 and not Sm32. The selectivity and
irreversibility of inactivation make
affinity labelling an invaluable tool
for exploring key differences among
closely related enzymes and also for
studying proteinase activity in a
cellular environment. In order to
confirm these results, we expressed
the complete cDNA sequences of Sm31
and Sm32 in insect cells and analysed
the recombinant gene products for
proteolytic activities. Cell extracts
containing S. mansoni cathepsin B, but
not those expressing 'haemoglobinase',
were demonstrated to cleave a
synthetic substrate
benzyloxycarbonyl-arginylarginylaminomethylcoumarin
in fluorescence assays. Our findings
confirm previous assertions that a
cysteine proteinase resembling
cathepsin B is the haemoglobinase
involved in digestion of host
proteins. Thus, the original proposal
that Sm32 is a cysteine proteinase has
not been verified, and its function
remains unknown.
- Language of Publication
- English
- Unique Identifier
- 93207533
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- MeSH Heading (Major)
- Cathepsin B|CH/*GE/ME; Cysteine
Endopeptidases|CH/*GE/ME; Gene
Expression|*; Helminth
Proteins|*GE/ME; Schistosoma mansoni|*EN
- MeSH Heading
- Amino Acid Sequence; Animal;
Baculoviridae|GE; Binding Sites; Cell
Line; Cloning, Molecular; Coumarins|ME;
Dipeptides|ME; Hemoglobins|ME;
Hydrolysis; Immunoblotting; Molecular
Sequence Data; Moths|ME; Recombinant
Proteins|CH/ME; Substrate Specificity;
Support, Non-U.S. Gov't; Transfection
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0264-6021
- Country of Publication
- ENGLAND
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- Title
- Exploration of subsite binding
specificity of human cathepsin D
through kinetics and rule-based
molecular modeling.
- Author
- Scarborough PE; Guruprasad K; Topham
C; Richo GR; Conner GE; Blundell TL;
Dunn BM
- Address
- Department of Biochemistry and
Molecular Biology, University of
Florida, Gainesville 32610.
- Source
- Protein Sci, 1993 Feb, 2:2, 264-76
- Abstract
- The family of aspartic proteinases
includes several human enzymes that
may play roles in both physiological
and pathophysiological processes. The
human lysosomal aspartic proteinase
cathepsin D is thought to function in
the normal degradation of
intracellular and endocytosed proteins
but has also emerged as a prognostic
indicator of breast tumor
invasiveness. Presented here are
results from a continuing effort to
elucidate the factors that contribute
to specificity of ligand binding at
individual subsites within the
cathepsin D active site. The synthetic
peptide Lys-Pro-Ile-Glu-Phe*Nph-Arg-Leu
has proven to be an excellent
chromogenic substrate for cathepsin D
yielding a value of kcat/Km = 0.92 x
10(-6) s-1 M-1 for enzyme isolated
from human placenta. In contrast, the
peptide Lys-Pro-Ala-Lys-Phe*Nph-Arg-Leu
and all derivatives with Ala-Lys in
the P3-P2 positions are either not
cleaved at all or cleaved with
extremely poor efficiency. To explore
the binding requirements of the S3 and
S2 subsites of cathepsin D, a series
of synthetic peptides was prepared
with systematic replacements at the P2
position fixing either Ile or Ala in
P3. Kinetic parameters were determined
using both human placenta cathepsin D
and recombinant human fibroblast
cathepsin D expressed in Escherichia
coli. A rule-based structural model of
human cathepsin D, constructed on the
basis of known three-dimensional
structures of other aspartic
proteinases, was utilized in an effort
to rationalize the observed substrate
selectivity.
- Language of Publication
- English
- Unique Identifier
- 93184744
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- MeSH Heading (Major)
- Cathepsin D|CH/GE/*ME; Chromogenic
Compounds|CH/*ME; Oligopeptides|CH/*ME
- MeSH Heading
- Amino Acid Sequence; Aspartic
Endopeptidases|ME; Computer
Simulation; Escherichia coli|GE;
Fibroblasts|EN; Human; Kinetics;
Models, Molecular; Molecular Sequence
Data; Placenta|EN; Protease
Inhibitors|ME; Recombinant Proteins|ME;
Structure-Activity Relationship;
Substrate Specificity; Support,
Non-U.S. Gov't; Support, U.S. Gov't,
P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0961-8368
- Country of Publication
- UNITED STATES
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- Title
- Cathepsin B expression in human
tumors.
- Author
- Berquin IM; Sloane BF
- Address
- Wayne State University, Department
of Pharmacology, Detroit, Michigan
48201, USA.
- Source
- Adv Exp Med Biol, 1996, 389:, 281-94
- Abstract
- Cathepsin B has been linked to tumor
progression through observations that
its activity, secretion or membrane
association are increased. The most
malignant tumors, and specifically the
cells at the invasive edge of those
tumors, express the highest activity.
Cathepsin B may facilitate invasion
directly by dissolving extracellular
matrix barriers like the basement
membrane, or indirectly by activating
other proteases capable of digesting
the extracellular matrix. Cathepsin B
also might play a role in tumor growth
and angiogenesis. Cathepsin B activity
is the result of several levels of
regulation: transcription,
post-transcription processing,
translation and glycosylation,
maturation and trafficking, and
inhibition. The majority of reports on
cathepsin B expression in tumors have
focused on measurements of activity or
protein staining. In some tumors, e.g.
gliomas, a correlation between the
amounts of cathepsin B mRNA, protein
and activity and tumor progression has
been established. Regulation of
cathepsin B at the transcriptional and
post-transcriptional levels is still
poorly understood. Although the
putative promoter regions have
characteristics of housekeeping-type
promoters, cathepsin B mRNA expression
varies depending on the cell type and
state of differentiation. We have
evidence that more than one promoter
could direct expression of human
cathepsin B. Multiple transcript
species have been detected, resulting
from alternative splicing in the 5'-
or 3'-untranslated regions, and
possibly the use of alternative
promoter regions. The existence of
transcript variants indicates a
potential for post-transcriptional
control of expression. In support of
this, ras-transformation of MCF-10A
human breast epithelial cells results
in an increase in protein levels
without a concomitant increase in mRNA
levels. Cathepsin B mRNA species with
distinct 5'- or 3'-untranslated
regions may differ in their stability
and translatability. Variations in the
coding region may also alter cathepsin
B properties. We and Frankfater's
group have observed transcript species
that would encode a truncated protein,
lacking the prepeptide and about half
of the propeptide. This truncated
protein, if synthesized in cells,
would be expected to be cytosolic;
therefore its function is unclear.
Once the several mechanisms of
regulation of cathepsin B expression
and activity are better understood,
they could provide us with new
strategies to specifically reduce
cathepsin B activity in tumors.
- Language of Publication
- English
- Unique Identifier
- 97014187
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- MeSH Heading (Major)
- Cathepsin B|*BI/GE; Neoplasms|*EN/PA;
Tumor Markers, Biological|*AN
- MeSH Heading
- Disease Progression; Gene Expression
Regulation, Neoplastic|PH; Human;
Organ Specificity; RNA, Messenger|GE;
Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW,
TUTORIAL
- ISSN
- 0065-2598
- Country of Publication
- UNITED STATES
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- Title
- Thrombin- and cathepsin G-induced
platelet aggregation: effect of
protein kinase C inhibitors.
- Author
- Puri RN; Colman RW
- Address
- Sol Sherry Thrombosis Research
Center, Temple University School of
Medicine, Philadelphia, Pennsylvania
19140.
- Source
- Anal Biochem, 1993 Apr, 210:1, 50-7
- Abstract
- Two serine proteases, thrombin and
cathepsin G, are potent agonists of
human platelet activation. These
pathophysiological proteases induce
similar platelet responses, e.g.,
aggregation, shape change, and
secretion of the dense granules.
Maintenance of proteolytic function
and the ability to bind to receptors
on the platelet surface membrane are
required for the responses elicited by
both proteases. Protein kinase C (PKC)
is a signal-transducing enzyme that is
an important regulator of postreceptor
intracellular changes following
exposure of platelets to thrombin and
cathepsin G. Inhibitors of purified
PKC, e.g., staurosporine and
calphostin C, have been frequently
used to elucidate biochemical
mechanisms mediated by the
intracellular PKC following platelet
activation by proteases. However, the
effect of the PKC inhibitors on the
amidolytic activity and on the ability
of the two bioregulatory proteases to
bind to cells has never been
investigated. We found that
staurosporine (1 and 1.5 microM),
calphostin C (10 and 60 microM), and
fisetin (200 and 220 microM), the
three most commonly used and
biochemically well-characterized
inhibitors of purified PKC, completely
inhibited thrombin-induced (2 nM) and
cathepsin G-induced (0.85 microM)
aggregation of washed human platelets,
respectively. Each of the three PKC
inhibitors completely blocked platelet
shape change induced by thrombin (1 nM).
Only fisetin inhibited platelet shape
change induced by cathepsin G (0.5
microM). Only fisetin partially
inhibited amidolytic activity of
thrombin. The three PKC inhibitors had
no inhibitory effect on the amidolytic
activity of those concentrations of
cathepsin G that cause maximum
platelet aggregation and platelet
shape change. The three PKC inhibitors
completely blocked binding of
125I-thrombin to washed
platelets.(ABSTRACT TRUNCATED AT 250
WORDS)
- Language of Publication
- English
- Unique Identifier
- 93256284
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- MeSH Heading (Major)
- Cathepsins|ME/*PD; Platelet
Aggregation|*DE/PH; Protein Kinase
C|*AI/PH; Thrombin|ME/*PD
- MeSH Heading
- Alkaloids|PD; Amino Acid Sequence;
Blood Platelets|CY/DE/ME; Flavones|PD;
Human; In Vitro; Molecular Sequence
Data; Oligopeptides|CH; Polycyclic
Hydrocarbons|PD; Substrate
Specificity; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0003-2697
- Country of Publication
- UNITED STATES
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- Title
- Processing of beta-amyloid precursor
protein by cathepsin D.
- Author
- Higaki J; Catalano R; Guzzetta AW;
Quon D; Navé JF; Tarnus C; DOrchymont
H; Cordell B
- Address
- Scios, Inc., Mountain View,
California 94043, USA.
- Source
- J Biol Chem, 1996 Dec, 271:50,
31885-93
- Abstract
- The events leading to the formation
of beta-amyloid (betaA4) from its
precursor (betaAPP) involve
proteolytic cleavages that produce the
amino and carboxyl termini of betaA4.
The enzyme activities responsible for
these cleavages have been termed beta-
and gamma-secretase, respectively,
although these protease(s) have not
been identified. Since betaA4 is known
to possess heterogeneity at both the
amino and carboxyl termini, beta- and
gamma-secretases may actually be a
collection of proteolytic activities
or perhaps a single proteolytic enzyme
with broad amino acid specificity. We
investigated the role of cathepsin D
in the processing of betaAPP since
this enzyme has been widely proposed
as a gamma-secretase candidate.
Treatment of a synthetic peptide that
spans the gamma-secretase site of
betaAPP with human cathepsin D
resulted in the cleavage of this
substrate at Ala42-Thr43. A sensitive
liquid chromatography/mass
spectrometry technique was also
developed to further investigate the
ability of cathepsin D to process
longer recombinant betaAPP substrates
(156 and 100 amino acids of betaAPP
carboxyl terminus) in vitro. The
precise cathepsin D cleavage sites
within these recombinant betaAPP
substrates were identified using this
technique. Both recombinant substrates
were cleaved at the following sites:
Leu49-Val50, Asp68-Ala69, Phe93-Phe94.
No cleavages were observed at putative
gamma-secretase sites: Val40-Ile41 or
Ala42-Thr43, suggesting that cathepsin
D is not gamma-secretase as defined by
these betaA4 termini. Under conditions
where the betaAPP156 substrate was
first denatured prior to cathepsin D
digestion, two additional cleavage
sites near the amino terminus of
betaA4, Glu-3-Val-2 and Glu3-Phe4,
were observed, indicating that
cathepsin D cleavage of betaAPP is
influenced by the structural integrity
of the substrate. Taken together,
these results indicate that in vitro,
cathepsin D is unlikely to function as
gamma-secretase; however, the ability
of this enzyme to efficiently cleave
betaAPP substrates at nonamyloidogenic
sites within the molecule may reflect
a role in betaAPP catabolism.
- Language of Publication
- English
- Unique Identifier
- 97112979
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- MeSH Heading (Major)
- Amyloid beta-Protein Precursor|*ME;
Cathepsin D|*ME
- MeSH Heading
- Amino Acid Sequence; Blotting,
Western; Chromatography, High Pressure
Liquid; Human; Molecular Sequence
Data; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9258
- Country of Publication
- UNITED STATES
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- Title
- Cathepsin D serum mass
concentrations in patients with
hepatocellular carcinoma and/or liver
cirrhosis.
- Author
- Leto G; Tumminello FM; Pizzolanti G;
Montalto G; Soresi M; Ruggeri I;
Gebbia N
- Address
- Servizio di Chemioterapia, FacoltÄa
di Medicina e Chirurgia, UniversitÄa
di Palermo, Italy.
- Source
- Eur J Clin Chem Clin Biochem, 1996
Jul, 34:7, 555-60
- Abstract
- Cathepsin D serum mass
concentrations were determined by
enzyme immunoassay in patients with
hepatocellular carcinoma (n = 51)
and/or liver cirrhosis (n = 92) or
benign steatosis (n = 16) and
correlated with some biochemical and
clinical properties of these diseases.
Increased cathepsin D serum mass
concentrations (P < 0.001) were
observed in all these groups of
patients as compared to normal
subjects (n = 98). However, patients
with steatosis had serum mass
concentrations of this enzyme
significantly lower (mean 2-3 fold)
than those measured in cancer patients
(P < 0.05) or cirrhotic patients (P
< 0.001). Interestingly,
significantly higher cathepsin D serum
mass concentrations (mean + 62%) (P
< 0.006) were determined in the
cirrhosis group as compared to cancer
patients. No correlation between
cathepsin D and a number of clinical
and biochemical properties examined,
namely, alpha-foetoprotein, number of
neoplastic lesions and tumour size in
cancer patients or, Child-Pugh grade
of severity of cirrhosis and other
enzymes of liver function tests in the
cirrhotic group was found. The present
data and those from other studies
which indicate that cathepsin D may be
involved in carcinogenesis suggest
that this enzyme may be potentially
useful as an additional biochemical
marker to identify cirrhotic patients
who may develop precancerous hepatic
nodules.
- Language of Publication
- English
- Unique Identifier
- 97017787
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- MeSH Heading (Major)
- Carcinoma, Hepatocellular|*EN;
Cathepsin D|*BL; Liver Cirrhosis|*EN;
Liver Neoplasms|*EN
- MeSH Heading
- alpha-Fetoproteins|AN; Adult; Aged;
Female; Hepatitis, Alcoholic|EN;
Human; Immunoenzyme Techniques; Male;
Middle Age; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0939-4974
- Country of Publication
- GERMANY
Record 54 from database:
MEDLINE
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- Title
- Cathepsin L proteinase secreted by
Fasciola hepatica in vitro prevents
antibody-mediated eosinophil
attachment to newly excysted
juveniles.
- Author
- Carmona C; Dowd AJ; Smith AM; Dalton
JP
- Address
- School of Biological Sciences,
Dublin City University, Glasnevin,
Ireland.
- Source
- Mol Biochem Parasitol, 1993 Nov,
62:1, 9-17
- Abstract
- Cathepsin L-like activity was
demonstrated in the excretory/secretory
(E/S) products of Fasciola hepatica
newly excysted juveniles (NEJ),
3-week-old, 5-week-old and mature
flukes using the fluorogenic
substituted 7-amino-4-methylcoumarin
substrates Z-phe-arg-AMC, Z-arg-arg-AMC
and Z-arg-AMC. Gelatin-substrate
polyacrylamide gel analysis revealed
that the E/S from each of these stages
contained multiple proteolytic
enzymes; however, the pattern of
proteinases obtained for NEJ E/S
differed markedly from that of all
other stages examined. The four NEJ
proteinases identified were inhibited
by leupeptin and Z-phe-ala-diazomethyl
ketone indicating that each had
cathepsin L-like activity. The E/S
products of all four developmental
stages contain an enzyme capable of
cleaving immunoglobulin at the hinge
region, the activity of which is also
inhibited by Z-phe-ala-diazomethyl
ketone. Using in vitro cell attachment
assays we show that the cathepsin
L-like proteinase purified from the
E/S products of adult F. hepatica can
prevent the antibody-mediated
attachment of eosinophil to NEJ. These
experiments indicate that this
proteinase has an important biological
function in immune evasion.
- Language of Publication
- English
- Unique Identifier
- 94158980
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- MeSH Heading (Major)
- Antibody-Dependent Cell Cytotoxicity|*;
Cathepsins|IM/ME/*SE; Eosinophils|CY/*IM;
Fasciola hepatica|*EN/GD/*IM
- MeSH Heading
- Animal; Cell Adhesion|IM; IgG|ME; In
Vitro; Substrate Specificity; Support,
Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0166-6851
- Country of Publication
- NETHERLANDS
Record 55 from database:
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- Title
- Structure, function, regulation and
clinical significance of the 52K pro-cathepsin
D secreted by breast cancer cells.
- Author
- Rochefort H; Augereau P; Briozzo P;
Capony F; Cavailles V; Freiss G;
Garcia M; Maudelonde T; Morisset M;
Vignon F
- Address
- UnitÆe Hormones et Cancer, INSERM U
148, Montpellier, France.
- Source
- Biochimie, 1988 Jul, 70:7, 943-9
- Abstract
- In estrogen-receptor-positive human
breast cancer cell lines (MCF7,
ZR75-1), estrogens specifically
increase the secretion into the
culture medium of a 52,000 Da (52K)
glycoprotein and stimulate cell
proliferation. The 52K protein has
been purified to homogeneity using
monoclonal antibodies and identified
as the secreted precursor of a
cathepsin D bearing
mannose-6-phosphate signals. The
secreted precursor 52K protein is
mitogenic in vitro in
estrogen-deprived MCF7 cells, can be
taken up by these cells via
mannose-6-phosphate receptors, and can
degrade extracellular matrix and
proteoglycans following its
auto-activation. The protease is also
produced constitutively by ER-negative
cell lines, and is inducible by
tamoxifen in some antiestrogen-resistant
variants. The corresponding cDNA has
been cloned using N-terminal
sequencing of the protein and
monoclonal antibodies. Its complete
sequencing indicates a strong homology
with pro-cathepsin D of normal
tissues. Using a cDNA probe, the
regulation of 52K cathepsin D mRNA by
estrogens and antiestrogens has been
studied and chromosome localization
determined by in situ hybridization.
Clinical studies using both
immunohistochemistry and
immunoenzymatic assay of breast cancer
cytosol have shown that the
concentration of total cellular
cathepsin D (52K + 48K + 34K) is
related to the proliferation of
mammary ducts and to the prognosis of
breast cancer. Its cytosolic
concentration in primary tumors of
postmenopausal patients is correlated
slightly with lymph node invasion and
significantly with shorter
disease-free intervals in a 6-year
retrospective study with the Danish
Breast Cancer Groups and Finsen
Institute (S. Thorpe et al.).(ABSTRACT
TRUNCATED AT 250 WORDS)
- Language of Publication
- English
- Unique Identifier
- 89088285
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- MeSH Heading (Major)
- Breast Neoplasms|DI/*EN; Cathepsin
D|GE/IP/*SE; Enzyme Precursors|GE/IP/*SE
- MeSH Heading
- Cell Line; Cell Transformation,
Neoplastic; Estrogens|PD; Female;
Human; Molecular Weight; Prognosis;
Protein Processing, Post-Translational;
Support, Non-U.S. Gov't; Translation,
Genetic; Tumor Markers, Biological|AN
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0300-9084
- Country of Publication
- FRANCE
Record 56 from database:
MEDLINE
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- Title
- Endometrial cathepsin D
immunostaining throughout ovulatory
and anovulatory menstrual cycles.
- Author
- Camier B; Hedon B; Rochefort H;
Maudelonde T
- Address
- Department of Reproductive Biology,
Hopital d'Amiens, France.
- Source
- Hum Reprod, 1996 Feb, 11:2, 392-7
- Abstract
- The results of histological
examination of the endometrium are
normal in most patients with
unexplained sterility. Cathepsin D is
a ubiquitous lysosomal protease
regulated by progesterone in the
endometrium. Assays of concentrations
of cathepsin D might be useful in
determining the functional responses
of the endometrium to progesterone. To
examine this possibility, we
quantified immunostaining of
endometrial cathepsin D using an image
analysis system in women with regular
menstrual cycles. An endometrial
sample was obtained during the
proliferative and luteal phases from
17 women with ovulatory menstrual
cycles and at the beginning and during
the last 14 days of a cycle from 15
women having anovulatory menstrual
cycles. In endometrial glands of
ovulatory women, cathepsin D protein
immunostaining increased during the
cycle and was significantly higher
during the luteal than during the
proliferative phase [51 +/- 38.1
arbitrary units (AU) versus 118.2 +/-
58.9 AU; P < 0.01]. This increase
was also observed in stromal cells,
although to a lesser extent (28.6 +/-
26.9 versus 41.5 +/- 43.1 AU; P = NS).
In the endometrium of women with
anovulatory menstrual cycles,
cathepsin D staining was high both for
the proliferative and the luteal
biopsies in glands (respectively 95
+/- 43 and 104 +/- 51.3 AU) and
stromal cells (respectively 61.8 +/-
33.8 and 75 +/- 32.6 AU). In women
with ovulatory cycles, cathepsin D
staining was localized in the apical
part of glandular cells during the
proliferative phase and diffused
throughout the cytoplasm during the
luteal phase. In contrast, in women
with anovulatory cycles, cellular
localization of cathepsin D remained
apical in glands, regardless of the
day of biopsy. In conclusion, this
study shows that the cytoplasmic
localization of cathepsin D might be a
qualitative biological indicator of
endometrial gland responses to
progesterone. This could be a useful
tool for evaluating cell function,
which is poorly tested by histology
alone.
- Language of Publication
- English
- Unique Identifier
- 96256930
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- MeSH Heading (Major)
- Anovulation|*PP; Cathepsin D|*ME;
Endometrium|CY/*ME; Menstrual Cycle|*;
Ovulation|*
- MeSH Heading
- Adult; Female; Human;
Immunohistochemistry; Staining;
Support, Non-U.S. Gov't; Tissue
Distribution
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