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