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Record 1
from database: MEDLINE
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- Title
- Effect of metal chelators and
antiinflammatory drugs on the degradation
of hyaluronic acid.
- Author
- Betts WH; Cleland LG
- Address
-
- Source
- Arthritis Rheum, 1982 Dec, 25:12,
1469-76
- Abstract
- Degradation of hyaluronic acid (measured
viscometrically) by oxygen-derived free
radicals (ODFR) generated 1) by
autoxidation of ferrous EDTA chelates and
2) enzymatically by xanthine oxidase and
hypoxanthine (XO/HX) was studied.
Degradation of hyaluronic acid by XO/HX
was strongly inhibited by superoxide
dismutase and catalase, whereas
degradation of hyaluronic acid by
autoxidation of ferrous ions was weakly
inhibited by catalase and unaffected by
superoxide dismutase. Both ODFR-producing
systems were inhibited by hydroxyl radical
scavengers, suggesting that hydroxyl
radical was the proximate damaging species
in both systems. Penicillamine at
concentrations of 1-5 mM stimulated
hyaluronic acid degradation by ferrous
EDTA chelates but inhibited degradation by
the XO/HX system. Higher concentrations of
penicillamine and all concentrations
studied (1-100 mM) of other
antiinflammatory drugs (chloroquine, gold
sodium thiomalate, and salicylate)
inhibited hyaluronic acid degradation by
both the autoxidation and enzymatic ODFR-producing
systems, with inhibitory potency similar
to that seen with known hydroxyl radical
scavengers. Both systems serve as in vitro
models of ODFR-mediated tissue damage
which may occur in vivo at sites of
inflammation.
- Language of Publication
- English
- Unique Identifier
- 83074853
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- MeSH Heading (Major)
- Anti-Inflammatory Agents|*PD; Hyaluronic
Acid|*ME; Iron Chelating Agents|*PD
- MeSH Heading
- Animal; Catalase|PD; Cattle; Edetic
Acid|PD; Human; Hypoxanthines|PD;
Oxidation-Reduction; Superoxide
Dismutase|PD; Support, Non-U.S. Gov't;
Time Factors; Viscosity; Xanthine
Oxidase|PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0004-3591
- Country of Publication
- UNITED STATES
Record 2
from database: MEDLINE
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- Title
- Relationship between metal toxicity to
subcellular systems and the carcinogenic
response.
- Author
- Squibb KS; Fowler BA
- Address
-
- Source
- Environ Health Perspect, 1981 Aug, 40:,
181-8
- Abstract
- The effects of metals on subcellular
organelle functions have been reviewed in
relation to carcinogenesis. Perturbations
of the normal uptake and metabolism of
carcinogens can arise through changes in
microsomal enzyme activities, membrane
permeabilities, and cell turnover. Metal
effects on heme-dependent oxidative
functions are well documented and are
primarily manifested by increased heme
degradation rates (microsomal heme
oxygenase activity), decreased heme
production (mitochondrial and cytosolic
heme biosynthetic enzymes) and, in the
case of a few metals, through nuclear
effects of metals on the induction of
microsomal enzymes. Many metals are
accumulated by lysosomes, but known
effects of metals on the function of these
organelles in sequestering and storing
organic compounds are few. Studies of
changes in plasma or mitochondrial
membrane permeabilities by metals have
centered mainly on the susceptibility of
membrane ATPase activities to metal ion
alteration and on the involvement of
metals in lipid peroxidation and free
radical formation. Knowledge of the
effects of metals on subcellular organelle
functions should aid in the understanding
of the mechanisms by which metal ions may
play a role in the carcinogenic response.
- Language of Publication
- English
- Unique Identifier
- 82004104
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- MeSH Heading (Major)
- Metals|*AE; Neoplasms|*CI/UL
- MeSH Heading
- Animal; Cell Membrane|DE; Cell
Nucleus|DE; Endoplasmic Reticulum|DE;
Human; Lysosomes|DE; Microsomes|DE;
Mitochondria|DE; Proteins|BI
- Publication Type
- JOURNAL ARTICLE; REVIEW
- ISSN
- 0091-6765
- Country of Publication
- UNITED STATES
Record 3
from database: MEDLINE
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- Title
- The importance of free radicals and
catalytic metal ions in human diseases.
- Author
- Halliwell B; Gutteridge JM
- Address
-
- Source
- Mol Aspects Med, 1985, 8:2, 89-193
- Abstract
- The study of free radical reactions is
not an isolated and esoteric branch of
science. A knowledge of free radical
chemistry and biochemistry is relevant to
an understanding of all diseases and the
mode of action of all toxins, if only
because diseased or damaged tissues
undergo radical reactions more readily
than do normal tissues. However it does
not follow that because radical reactions
can be demonstrated, they are important in
any particular instance. We hope that the
careful techniques needed to assess the
biological role of free radicals will
become more widely used.
- Language of Publication
- English
- Unique Identifier
- 86091331
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- MeSH Heading (Major)
- Disease|*ME; Free Radicals|*; Metals|*ME
- MeSH Heading
- Aging; Autoimmune Diseases|ME; Brain
Ischemia|ME; Copper|ME; Coronary
Disease|ME; Exertion; Human; Intestines|BS;
Iron|ME; Ischemia|ME; Joint Diseases|ME;
Lipid Peroxides; Malaria|ME; Neoplasms|ME;
Nervous System Diseases|ME; Respiratory
Distress Syndrome, Adult|ME; Support,
Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE; REVIEW
- ISSN
- 0098-2997
- Country of Publication
- UNITED STATES
Record 4
from database: MEDLINE
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- Title
- Electron spin resonance investigation of
laser and heated metal-tip-induced free
radical formation in various tissues.
- Author
- Jain S; Shi X; Billie M; Jain AC; Dalal
NS
- Address
- Department of Chemistry, West Virginia
University, Morgantown 26506.
- Source
- Lasers Surg Med, 1989, 9:6, 616-22
- Abstract
- The short-lived free radical formation
accompanying laser irradiation and
laser-heated metal tip contact was
examined using electron spin resonance (ESR)
spin-trap methodology. Various tissues
(canine myocardium, human aorta, liver,
and spleen) were irradiated by argon-ion
(continuous wave [CW] and pulse) and YAG (CW)
lasers employing both naked fiber and a
laser-heated metal tip. All showed the
formation of primarily carbon-centered,
not oxygenated, free radicals, together
with some minor unidentified species. This
implies that the backbones of amino acids,
lipids, or other biological building
blocks are cleaved during the irradiation
or thermal treatment. Different tissues
produce similar radicals but with
different amounts when irradiated by
argon-ion, YAG, and laser-heated metal tip
sources. The amount of the free radicals
formed depends on the laser power (within
5-15 W). Compared to the naked fiber, the
laser-heated metal tip shows the
generation of at least twice the amount of
free radicals. The possible relationship
of the free radical formation to tissue
injury is briefly discussed.
- Language of Publication
- English
- Unique Identifier
- 90097468
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- MeSH Heading (Major)
- Carbon|*AN; Electron Spin Resonance
Spectroscopy|*IS; Laser Surgery|*IS;
Nuclear Magnetic Resonance|*IS; Signal
Processing, Computer-Assisted|*
- MeSH Heading
- Animal; Aorta|AN; Dogs; Free Radicals;
Human; Liver|AN; Microcomputers;
Myocardium|AN; Spleen|AN
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0196-8092
- Country of Publication
- UNITED STATES
Record 5
from database: MEDLINE
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- Title
- Study of antioxidant properties of metal
aspartates.
- Author
- Afanasev IB; Suslova TB; Cheremisina ZP;
Abramova NE; Korkina LG
- Address
- Russian Institute for Pediatric
Hematology, Moscow.
- Source
- Analyst, 1995 Mar, 120:3, 859-62
- Abstract
- The effects of Zn, Mg, Cr, Cu, and Mn
aspartates, their commercial formulation
Inzolen, and the individual commercial
medicine Unizinc, on oxygen radical
production by enzymes [xanthine oxidase,
horseradish peroxidase, and reduced
nicotinamide adenine dinucleotide
phosphate (NADPH) oxidase] and phagocytic
cells (human blood leukocytes) have been
studied. The formation of oxygen radicals
was measured by luminol- and lucigenin-amplified
chemiluminescence and by the reduction of
cytochrome c. All these compounds
(excluding Cr aspartate) turn out to be
inhibitors of oxygen radical formation in
the systems studied (excluding horseradish
peroxidase). Their inhibitory activities
were a consequence of both the scavenging
of free radicals and the inhibition of
xanthine oxidase and NADPH oxidase
activities. As expected, the most active
free-radical scavengers were transition
metal Cu and Mn aspartates, which mimicked
the activities of copper-zinc and
manganese dismutases. However,
surprisingly non-transition metal Zn and
Mg aspartates were also able to scavenge
oxygen radicals. It was suggested that the
scavenging activities of Zn and Mg
aspartates may be explained by affecting
the rate of spontaneous dismutation of the
superoxide ion. In addition, it was found
that Zn aspartate is an efficient
inhibitor of the formation of the most
reactive hydroxyl radicals. These
antioxidant properties of Zn aspartate
make it important in medicine for the
prevention and treatment of free radical
pathologies.
- Language of Publication
- English
- Unique Identifier
- 95259809
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- MeSH Heading (Major)
- Antioxidants|*PD; Aspartic Acid|*AA/PD;
Metals|*PD
- MeSH Heading
- Free Radical Scavengers; Free Radicals;
Human; Leukocytes|DE/ME; Magnesium|PD;
Reactive Oxygen Species|ME; Superoxides|BL;
Zinc|PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0003-2654
- Country of Publication
- ENGLAND
Record 6
from database: MEDLINE
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- Title
- Metal ions catalytic for free radical
reactions in the plasma of patients with
fulminant hepatic failure.
- Author
- Evans PJ; Evans RW; Bomford A; Williams
R; Halliwell B
- Address
- Pharmacology Group, University of London
King's College, UK.
- Source
- Free Radic Res, 1994 Mar, 20:3, 139-44
- Abstract
- We propose that the frequency and
severity of multi-organ failure (MOF) in
fulminant hepatic failure (FHF) involves
free radical damage caused by the presence
of circulating iron and copper ions,
catalytic for free radical reactions. The
presence of such metal ions is
demonstrated by using the sensitive
bleomycin and phenanthroline assays.
Antioxidant therapy, e.g., using chelating
agents that prevent metal ions from
stimulating free radical reactions, may
have benefit in the treatment of FHF and
its consequences.
- Language of Publication
- English
- Unique Identifier
- 94290593
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- MeSH Heading (Major)
- Copper|*BL; Hepatic Encephalopathy|*BL;
Iron|*BL
- MeSH Heading
- Acetaminophen|PO; Adult; Aged;
Antioxidants|TU; Chelating Agents|TU;
Female; Free Radicals|ME; Hepatitis|CO;
Human; Indicators and Reagents; Lipid
Peroxidation; Male; Middle Age; Multiple
Organ Failure|PP; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 1071-5762
- Country of Publication
- SWITZERLAND
Record 7
from database: MEDLINE
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- Title
- Regulation of human neutrophil guanylate
cyclase by metal ions, free radicals and
the muscarinic cholinergic receptor.
- Author
- Lad PM; Glovsky MM; Richards JH; Smiley
PA; Backstrom B
- Address
-
- Source
- Mol Immunol, 1985 Jul, 22:7, 731-9
- Abstract
- We have examined the properties of
soluble guanylate cyclase activity in the
human neutrophil. The enzyme showed
complex regulation by metal ions. A
10-fold higher activity was observed in
the presence of Mn2+ than Mg2+, while Ca2+
caused an increase in activity only in the
presence of Mg2+ ion. Sodium nitroprusside
(SNP), azide and hydrogen peroxide were
activators of the enzyme. Dithiothreitol
blocked the activation by SNP, suggesting
the involvement of thiol groups in the
activation process. Carbachol acting
through the muscarinic cholinergic
receptor caused a dose-dependent
activation, which was blocked by atropine.
Higher concns of carbachol were required
to activate guanylate cyclase than were
required for the modulation of enzyme
release elicited by N-formyl-L-methionyl-L-leucyl-L-phenylalanine.
Nordihydroguaracetic acid inhibited
carbachol stimulation of guanylate cyclase.
By contrast, trifluoperazine (TFP), a
calmodulin antagonist, caused a biphasic
modulation of basal activity in the
presence or absence of carbachol. Our
results indicate that: allosteric
interactions of metal ions are important
to the regulation of the enzyme, the free
radical nitroxide as well as hydrogen
peroxide enhances enzyme activity, agonist
occupancy of the muscarinic cholinergic
receptor activates neutrophil guanylate
cyclase probably through a mechanism
involving calcium influx and the
activation of the lipoxygenase pathway,
and a TFP-sensitive site (possibly
calmodulin) is involved in the selective
regulation of basal enzyme activity.
- Language of Publication
- English
- Unique Identifier
- 85296012
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- MeSH Heading (Major)
- Guanylate Cyclase|AI/*BL; Metals|*PD;
Neutrophils|*EN; Receptors, Muscarinic|*ME
- MeSH Heading
- Azides|PD; Calcium|PD; Carbachol|PD;
Catalase|ME; Dithiothreitol|PD;
Dose-Response Relationship, Drug; Enzyme
Activation|DE; Free Radicals; Human;
Hydrogen Peroxide|PD; Magnesium|PD;
Manganese|PD; Nitroprusside|PD; Support,
Non-U.S. Gov't; Support, U.S. Gov't,
P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0161-5890
- Country of Publication
- ENGLAND
Record 8
from database: MEDLINE
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- Title
- Metal ion-catalyzed oxidation of
proteins: biochemical mechanism and
biological consequences [published erratum
appears in Free Radic Biol Med
1991;10(3-4):249]
- Author
- Stadtman ER
- Address
- Laboratory of Biochemistry, National
Heart, Lung, and Blood Institute, National
Institutes of Health, Bethesda, MD 20892.
- Source
- Free Radic Biol Med, 1990, 9:4, 315-25
- Abstract
- In the presence of O2, Fe(III) or Cu(II),
and an appropriate electron donor, a
number of enzymic and nonenzymic oxygen
free radical-generating systems are able
to catalyze the oxidative modification of
proteins. Whereas random, global
modification of many different amino acid
residues and extensive fragmentation
occurs when proteins are exposed to oxygen
radicals produced by high energy
radiation, only one or a few amino acid
residues are modified and relatively
little peptide bond cleavage occurs when
proteins are exposed to metal-catalyzed
oxidation (MCO) systems. The available
evidence indicates that the MCO systems
catalyze the reduction of Fe(III) to Fe(II)
and of O2 to H2O2 and that these products
react at metal-binding sites on the
protein to produce active oxygen (free
radical?) species (viz; OH, ferryl ion)
which attack the side chains of amino acid
residues at the metal-binding site. Among
other modifications, carbonyl derivatives
of some amino acid residues are formed;
prolyl and arginyl residues are converted
to glutamylsemialdehyde residues, lysyl
residues are likely converted to
2-amino-adipylsemialdehyde residues;
histidyl residues are converted to
asparagine and/or aspartyl residues;
prolyl residues are converted to glutamyl
or pyroglutamyl residues; methionyl
residues are converted to
methionylsulfoxide residues; and cysteinyl
residues to mixed-disulfide derivatives.
The biological significance of these metal
ion-catalyzed reactions is highlighted by
the demonstration: (i) that oxidative
modification of proteins "marks"
them for degradation by most common
proteases and especially by the cytosolic
multicatalytic proteinase from mammalian
cells; (ii) protein oxidation contributes
substantially to the intracellular pool of
catalytically inactive and less active,
thermolabile forms of enzymes which
accumulate in cells during aging,
oxidative stress, and in various
pathological states, including premature
aging diseases (progeria, Werner's
syndrome), muscular dystrophy, rheumatoid
arthritis, cataractogenesis, chronic
alcohol toxicity, pulmonary emphysema, and
during tissue injury provoked by
ischemia-reperfusion. Furthermore, the
metal ion-catalyzed protein oxidation is
the basis of biological mechanisms for
regulating changes in enzyme levels in
response to shifts from anaerobic to
aerobic metabolism, and probably from one
nutritional state to another. It is also
involved in the killing of bacteria by
neutrophils and in the loss of neutrophil
function following repeated cycles of
respiratory burst activity.
- Language of Publication
- English
- Unique Identifier
- 91131022
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- MeSH Heading (Major)
- Copper|*ME; Ferrous Compounds|*ME;
Oxygen|*ME; Proteins|*ME
- MeSH Heading
- Aging; Animal; Free Radicals; Human;
Oxidation-Reduction
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW,
ACADEMIC
- ISSN
- 0891-5849
- Country of Publication
- UNITED STATES
Record 9
from database: MEDLINE
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- Title
- Free radicals as potential mediators of
metal allergy: effect of ascorbic acid on
lymphocyte proliferation and IFN-gamma
production in contact allergy to Ni2+ and
Co2+.
- Author
- Van Den Broeke LT; Gräslund A; Larsson
PH; Nilsson JL; Wahlberg JE; Scheynius A;
Karlberg AT
- Address
- Department of Occupational Health,
National Institute for Working Life, Solna,
Sweden.
- Source
- Acta Derm Venereol, 1998 Mar, 78:2, 95-8
- Abstract
- A possible free radical mechanism in
metal allergy was investigated in
peripheral blood mononuclear cell (PBMC)
cultures from 6 subjects, contact allergic
to Ni2+ and Co2+, and 6 control
individuals. Ni2+ and Co(2+)-mediated free
radical generation was studied with
electron spin resonance spectroscopy. The
immune response was characterized by
cellular [methyl-3H]thymidine uptake and
interferon-gamma (IFN-gamma) production
Ni2+ and Co2+ (10-50 microM) significantly
increased lymphocyte proliferation and IFN-gamma
production in PBMC cultures from contact
allergic subjects in comparison with
cultures from controls. Inhibition of
Co(2+)-mediated free radical generation by
ascorbic acid did not influence cellular
[methyl-3H]thymidine uptake and IFN
production. Detectable amounts of free
radicals were not obtained with Ni2+. We
therefore conclude that it is unlikely
that free radicals are involved in contact
allergy to Ni2+ and Co2+.
- Language of Publication
- English
- Unique Identifier
- 98196383
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- MeSH Heading (Major)
- Ascorbic Acid|*PD; Copper|*AE;
Dermatitis, Allergic Contact|*IM;
Interferon Type II|*BI/DE; Monocytes|DE/*IM;
Nickel|*AE
- MeSH Heading
- Adult; Case-Control Studies; Cell
Culture; Electron Spin Resonance
Spectroscopy; Female; Free Radicals|IM;
Human; Middle Age; Patch Tests; Support,
Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0001-5555
- Country of Publication
- NORWAY
Record 10
from database: MEDLINE
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- Title
- Ascorbic acid oxidation product(s)
protect human low density lipoprotein
against atherogenic modification. Anti-
rather than prooxidant activity of vitamin
C in the presence of transition metal
ions.
- Author
- Retsky KL; Freeman MW; Frei B
- Address
- Department of Nutrition, Harvard School
of Public Health, Boston, Massachusetts
02115.
- Source
- J Biol Chem, 1993 Jan, 268:2, 1304-9
- Abstract
- The oxidative modification of low
density lipoprotein (LDL) has been
proposed as an important causative event
in the development of human
atherosclerosis. As a corollary of this
hypothesis, antioxidants that can prevent
LDL oxidation may inhibit atherosclerosis.
Oxidative modification of LDL in vitro,
either induced by Cu2+ or mediated by
cultured arterial wall cells in media
containing trace amounts of transition
metal ions, is strongly inhibited by
vitamin C (L-ascorbic acid (AA)). AA,
however, is known to act as a prooxidant
rather than an antioxidant in the presence
of transition metal ions. We observed that
AA is oxidized rapidly when incubated with
Cu2+ and LDL, leading to transient
formation of dehydro-L-ascorbic acid (DHA).
Although AA and DHA can no longer be
detected after 3.5 h of incubation, LDL
resists oxidative modification for at
least 20 h, as assessed by anodic gel
electrophoretic mobility. Remarkably, DHA
protects LDL more effectively against both
Cu(2+)-induced lipid peroxidation and
shifts in electrophoretic mobility than
does AA; indeed, AA per se, without
oxidation to DHA, offers no protection. By
inhibiting oxidative modification of LDL,
AA and DHA prevent uptake of LDL by
macrophages via the scavenger receptor
pathway. When LDL is incubated with DHA
followed by gel filtration, LDL remains
protected against subsequent
Cu(2+)-induced oxidative modification,
suggestive of stable modification of LDL
in the presence of DHA. In contrast, DHA
is ineffective against a metal
ion-independent type of oxidative stress,
viz. aqueous peroxyl radicals; under these
conditions, only AA is able to inhibit
lipid peroxidation in LDL. Our data
indicate that vitamin C protects LDL
against atherogenic modification by two
different mechanisms that may act in
concert: (i) free radical scavenging by AA
prevents aqueous oxidants from attacking
and oxidizing LDL, and (ii) stable
modification of LDL by DHA or
decomposition product(s) thereof imparts
increased resistance to metal
ion-dependent oxidation.
- Language of Publication
- English
- Unique Identifier
- 93123249
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- MeSH Heading (Major)
- Ascorbic Acid|*PD; Atherosclerosis|*BL;
Copper|*PD; Dehydroascorbic Acid|*PD;
Lipid Peroxidation|*; Lipoproteins,
LDL|*BL; Macrophages|*ME
- MeSH Heading
- Adult; Comparative Study; Female; Free
Radical Scavengers; Free Radicals; Human;
Male; Oxidation-Reduction; Pentetic
Acid|PD; Peroxides; Support, Non-U.S.
Gov't; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9258
- Country of Publication
- UNITED STATES
Record 11
from database: MEDLINE
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- Title
- Metal ion release from
mechanically-disrupted human arterial
wall. Implications for the development of
atherosclerosis.
- Author
- Evans PJ; Smith C; Mitchinson MJ;
Halliwell B
- Address
- Pharmacology Group, King's College,
London, UK.
- Source
- Free Radic Res, 1995 Nov, 23:5, 465-9
- Abstract
- Oxidation of low density lipoproteins
(LDL) in blood vessel walls plays a
significant role in the development of
atherosclerosis. LDL oxidation in vitro is
greatly accelerated by the presence of
"catalytic" iron or copper ions,
which have already been shown to be
present within advanced atherosclerotic
lesions. We demonstrate here that
mechanical damage to human arterial wall
samples (both normal and early or
intermediate atherosclerotic lesions)
causes release of "catalytic"
iron and copper ions, to an extent
increasing with the damage. It may be that
traumatic (e.g. during angioplasty) or
other injury to the vessel wall
contributes to the generation of metal
ions that can facilitate LDL oxidation and
other free radical reactions, so promoting
atherosclerosis.
- Language of Publication
- English
- Unique Identifier
- 96030029
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- MeSH Heading (Major)
- Arteries|*ME/*PA; Atherosclerosis|ME/PA/*PP;
Metals|*ME
- MeSH Heading
- Bleomycin; Comparative Study; Copper|AN/ME;
Free Radicals; Human; Indicators and
Reagents; Iron|AN/ME; Lipoproteins, LDL|ME;
Models, Cardiovascular; Muscle, Smooth,
Vascular|ME/PA; Oxidation-Reduction;
Phenanthrolines; Physical Stimulation;
Reference Values; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 1071-5762
- Country of Publication
- SWITZERLAND
Record 12
from database: MEDLINE
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- Title
- Ascorbic acid oxidation product(s)
protect human low density lipoprotein
against atherogenic modification. Anti-
rather than prooxidant activity of vitamin
C in the presence of transition metal
ions.
- Author
- Retsky KL; Freeman MW; Frei B
- Address
- Department of Nutrition, Harvard School
of Public Health, Boston, Massachusetts
02115.
- Source
- J Biol Chem, 1993 Jan, 268:2, 1304-9
- Abstract
- The oxidative modification of low
density lipoprotein (LDL) has been
proposed as an important causative event
in the development of human
atherosclerosis. As a corollary of this
hypothesis, antioxidants that can prevent
LDL oxidation may inhibit atherosclerosis.
Oxidative modification of LDL in vitro,
either induced by Cu2+ or mediated by
cultured arterial wall cells in media
containing trace amounts of transition
metal ions, is strongly inhibited by
vitamin C (L-ascorbic acid (AA)). AA,
however, is known to act as a prooxidant
rather than an antioxidant in the presence
of transition metal ions. We observed that
AA is oxidized rapidly when incubated with
Cu2+ and LDL, leading to transient
formation of dehydro-L-ascorbic acid (DHA).
Although AA and DHA can no longer be
detected after 3.5 h of incubation, LDL
resists oxidative modification for at
least 20 h, as assessed by anodic gel
electrophoretic mobility. Remarkably, DHA
protects LDL more effectively against both
Cu(2+)-induced lipid peroxidation and
shifts in electrophoretic mobility than
does AA; indeed, AA per se, without
oxidation to DHA, offers no protection. By
inhibiting oxidative modification of LDL,
AA and DHA prevent uptake of LDL by
macrophages via the scavenger receptor
pathway. When LDL is incubated with DHA
followed by gel filtration, LDL remains
protected against subsequent
Cu(2+)-induced oxidative modification,
suggestive of stable modification of LDL
in the presence of DHA. In contrast, DHA
is ineffective against a metal
ion-independent type of oxidative stress,
viz. aqueous peroxyl radicals; under these
conditions, only AA is able to inhibit
lipid peroxidation in LDL. Our data
indicate that vitamin C protects LDL
against atherogenic modification by two
different mechanisms that may act in
concert: (i) free radical scavenging by AA
prevents aqueous oxidants from attacking
and oxidizing LDL, and (ii) stable
modification of LDL by DHA or
decomposition product(s) thereof imparts
increased resistance to metal
ion-dependent oxidation.
- Language of Publication
- English
- Unique Identifier
- 93123249
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- MeSH Heading (Major)
- Ascorbic Acid|*PD; Atherosclerosis|*BL;
Copper|*PD; Dehydroascorbic Acid|*PD;
Lipid Peroxidation|*; Lipoproteins,
LDL|*BL; Macrophages|*ME
- MeSH Heading
- Adult; Comparative Study; Female; Free
Radical Scavengers; Free Radicals; Human;
Male; Oxidation-Reduction; Pentetic
Acid|PD; Peroxides; Support, Non-U.S.
Gov't; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9258
- Country of Publication
- UNITED STATES
Record 13
from database: MEDLINE
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- Title
- Transferrin C2, metal binding and
Alzheimer's disease.
- Author
- Van Landeghem GF; Sikström C; Beckman
LE; Adolfsson R; Beckman L
- Address
- Department of Medical Genetics, UmeÁa
University, Sweden.
- Source
- Neuroreport, 1998 Jan, 9:2, 177-9
- Abstract
- Significant associations between the
transferrin (TF) variant C2 and a number
of disorders suspected to be caused by
oxygen free radicals have been reported.
Thus an increased frequency of the TFC2
variant has been found in patients with
Alzheimer's disease (AD), and it has been
hypothesized that AD is caused by free
radical damage due to defective binding of
iron and aluminium by TFC2. In a study of
64 patients with AD from northern Sweden
we were able to confirm the association
between TFC2 and AD, but there were no
significant differences between TFC2 and
other TF variants with respect to the
binding of iron and aluminium.
- Language of Publication
- English
- Unique Identifier
- 98167369
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- MeSH Heading (Major)
- Alzheimer Disease|*ME; Metals|*ME;
Transferrin|*ME
- MeSH Heading
- Aluminum|ME; Free Radicals|ME; Human;
Iron|ME; Protein Binding
- Publication Type
- CLINICAL TRIAL; JOURNAL ARTICLE
- ISSN
- 0959-4965
- Country of Publication
- ENGLAND
Record 14
from database: MEDLINE
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- Title
- Metal ion transporters in mammals:
structure, function and pathological
implications.
- Author
- Rolfs A; Hediger MA
- Address
- Membrane Biology Program and Renal
Division, Department of Medicine, Brigham
& Women's Hospital, Boston, MA 02115,
USA. mhediger@rics.bwh.harvard.edu
- Source
- J Physiol (Lond), 1999 Jul, 518 ( Pt
1):, 1-12
- Abstract
- Despite the importance of metal ions in
several catalytic functions, there has
been, until recently, little molecular
information available on the mechanisms
whereby metal ions are actively taken up
by mammalian cells. The classical concept
for iron uptake into mammalian cells has
been the endocytosis of transferrin-bound
Fe3+ by the transferrin receptor. Studies
with hypotransferrinaemic mice revealed
that in the intestine mucosal transferrin
is derived from the plasma and that its
presence is not required in the intestinal
lumen for dietary iron absorption. This
suggests that, at least in the intestine,
other non-receptor-mediated uptake systems
exist. The molecular identification of
metal ion transporters is of great
importance, in particular since an
increasing number of human diseases are
thought to be related to disturbances in
metal ion homeostasis, including metal ion
overload and deficiency disorders (i.e.
anaemia, haemochromatosis, Menkes disease,
Wilson's disease), and neurodegenerative
diseases (i.e. Alzheimer's, Friedreich's
ataxia and Parkinson's diseases).
Furthermore, susceptibilities to
mycobacterial infections are caused by
metal ion transporter defects. The
pathological implications of disturbed
metal ion homeostasis confirm the vital
roles these metal ions play in the
catalytic function of many enzymes, in
gene regulation (zinc-finger proteins),
and in free radical homeostasis. Recent
insights have significantly advanced our
knowledge of how metal ions are taken up
or released by mammalian cells. The
purpose of this review is to summarize
these advances and to give an overview on
the growing number of mammalian metal ion
transporters.
- Language of Publication
- English
- Unique Identifier
- 99303709
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- MeSH Heading (Major)
- Carrier Proteins|CH/*ME/PH; Metals|*ME
- MeSH Heading
- Homeostasis|PH; Human
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW,
ACADEMIC
- ISSN
- 0022-3751
- Country of Publication
- ENGLAND
Record 15
from database: MEDLINE
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- Title
- Metal ion transporters in mammals:
structure, function and pathological
implications.
- Author
- Rolfs A; Hediger MA
- Address
- Membrane Biology Program and Renal
Division, Department of Medicine, Brigham
& Women's Hospital, Boston, MA 02115,
USA. mhediger@rics.bwh.harvard.edu
- Source
- J Physiol (Lond), 1999 Jul, 518 ( Pt
1):, 1-12
- Abstract
- Despite the importance of metal ions in
several catalytic functions, there has
been, until recently, little molecular
information available on the mechanisms
whereby metal ions are actively taken up
by mammalian cells. The classical concept
for iron uptake into mammalian cells has
been the endocytosis of transferrin-bound
Fe3+ by the transferrin receptor. Studies
with hypotransferrinaemic mice revealed
that in the intestine mucosal transferrin
is derived from the plasma and that its
presence is not required in the intestinal
lumen for dietary iron absorption. This
suggests that, at least in the intestine,
other non-receptor-mediated uptake systems
exist. The molecular identification of
metal ion transporters is of great
importance, in particular since an
increasing number of human diseases are
thought to be related to disturbances in
metal ion homeostasis, including metal ion
overload and deficiency disorders (i.e.
anaemia, haemochromatosis, Menkes disease,
Wilson's disease), and neurodegenerative
diseases (i.e. Alzheimer's, Friedreich's
ataxia and Parkinson's diseases).
Furthermore, susceptibilities to
mycobacterial infections are caused by
metal ion transporter defects. The
pathological implications of disturbed
metal ion homeostasis confirm the vital
roles these metal ions play in the
catalytic function of many enzymes, in
gene regulation (zinc-finger proteins),
and in free radical homeostasis. Recent
insights have significantly advanced our
knowledge of how metal ions are taken up
or released by mammalian cells. The
purpose of this review is to summarize
these advances and to give an overview on
the growing number of mammalian metal ion
transporters.
- Language of Publication
- English
- Unique Identifier
- 99303709
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- MeSH Heading (Major)
- Carrier Proteins|CH/*ME/PH; Metals|*ME
- MeSH Heading
- Homeostasis|PH; Human
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW,
ACADEMIC
- ISSN
- 0022-3751
- Country of Publication
- ENGLAND
Record 16
from database: MEDLINE
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- Title
- Cytokine production by human airway
epithelial cells after exposure to an air
pollution particle is metal-dependent.
- Author
- Carter JD; Ghio AJ; Samet JM; Devlin RB
- Address
- National Health and Environmental
Effects Research Laboratory, Environmental
Protection Agency, Research Triangle Park,
North Carolina 27711, USA.
- Source
- Toxicol Appl Pharmacol, 1997 Oct, 146:2,
180-8
- Abstract
- Despite the many epidemiological studies
supporting the contention that ambient air
pollution particles can adversely affect
human health, there is no clear agreement
as to a biologically plausible mechanism
which can explain the acute mortality and
morbidity associated with exposure to
particles less than 10 &mgr;m in size.
We tested the hypothesis that metals
present in an air pollution particle can
induce the synthesis and expression of the
inflammatory cytokines IL-8, IL-6, and
TNFalpha. A residual oil fly ash (ROFA)
containing the transition metals vanadium,
nickel, and iron was used as a model
emission source air pollution particle.
Normal human bronchial epithelial (NHBE)
cells were exposed for either 2 or 24 hr
to 0, 5, 50, or 200 microg/ml ROFA.
Concentrations of IL-8, IL-6, and TNF-alpha
proteins were measured with commercially
available ELISA kits. mRNA for these same
cytokines was quantified by RT-PCR. NHBE
cells exposed to ROFA produced significant
amounts of IL-8, IL-6, and TNF, as well as
mRNAs coding for these cytokines. Cytokine
production was inhibited by the inclusion
of either the metal chelator deferoxamine
(1.0 mM) or the free radical scavenger
dimethylthiourea (1.0 mM). In addition,
vanadium containing compounds, but not
iron or nickel sulfates, mimicked the
effects of intact ROFA. These results
demonstrate that metals present in ROFA
may be responsible for production and
release of inflammatory mediators by the
respiratory tract epithelium and suggest
that these mediators may contribute to the
toxic effects of particulate air
pollutants reported in epidemiology
studies. Copyright 1997 Academic Press.
- Language of Publication
- English
- Unique Identifier
- 98008957
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- MeSH Heading (Major)
- Air Pollutants, Occupational|*AE;
Bronchi|*DE/ME; Cytokines|*BI/GE;
Metals|*AE
- MeSH Heading
- Carbon|AE; Cells, Cultured; Chelating
Agents|PD; Deferoxamine|PD; Epithelial
Cells|DE/ME; Free Radical Scavengers|PD;
Human; Interleukin-6|BI/GE;
Interleukin-8|BI/GE; Iron|AE; Nickel|AE;
Particle Size; RNA, Messenger|AN/GE;
Thiourea|AA/PD; Tumor Necrosis Factor|BI/GE;
Vanadium|AE
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0041-008X
- Country of Publication
- UNITED STATES
Record 17
from database: MEDLINE
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- Title
- Cloning and characterization of a
mammalian proton-coupled metal-ion
transporter.
- Author
- Gunshin H; Mackenzie B; Berger UV;
Gunshin Y; Romero MF; Boron WF; Nussberger
S; Gollan JL; Hediger MA
- Address
- Renal Division, Department of Medicine,
Brigham & Women's Hospital and Harvard
Medical School, Boston, Massachusetts
02115, USA. hgunshin@rics.bwh.harvard.edu
- Source
- Nature, 1997 Jul, 388:6641, 482-8
- Abstract
- Metal ions are essential cofactors for a
wealth of biological processes, including
oxidative phosphorylation, gene regulation
and free-radical homeostasis. Failure to
maintain appropriate levels of metal ions
in humans is a feature of hereditary
haemochromatosis, disorders of metal-ion
deficiency, and certain neurodegenerative
diseases. Despite their pivotal
physiological roles, however, there is no
molecular information on how metal ions
are actively absorbed by mammalian cells.
We have now identified a new metal-ion
transporter in the rat, DCT1, which has an
unusually broad substrate range that
includes Fe2+, Zn2+, Mn2+, Co2+, Cd2+,
Cu2+, Ni2+ and Pb2+. DCT1 mediates active
transport that is proton-coupled and
depends on the cell membrane potential. It
is a 561-amino-acid protein with 12
putative membrane-spanning domains and is
ubiquitously expressed, most notably in
the proximal duodenum. DCT1 is upregulated
by dietary iron deficiency, and may
represent a key mediator of intestinal
iron absorption. DCT1 is a member of the
'natural-resistance-associated macrophage
protein' (Nramp) family and thus its
properties provide insight into how these
proteins confer resistance to pathogens.
- Language of Publication
- English
- Unique Identifier
- 97384897
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- MeSH Heading (Major)
- Carrier Proteins|GE/*ME; Membrane
Proteins|GE/*ME; Metals|*ME
- MeSH Heading
- Amino Acid Sequence; Animal; Cations,
Divalent; Cells, Cultured; Cloning,
Molecular; Human; Iron|DF/ME; Membrane
Potentials; Molecular Sequence Data;
Oocytes|ME; Organ Specificity; Rats; RNA,
Messenger|ME; Sequence Homology, Amino
Acid; Support, U.S. Gov't, P.H.S.; Xenopus
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0028-0836
- Country of Publication
- ENGLAND
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