Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rabbit liver metallothionein-1 (Mr 6500), which contains zinc and/or cadmium ions, appears to scavenge free hydroxyl (.OH) and superoxide (O-.2) radicals produced by the xanthine/xanthine oxidase reaction much more effectively than bovine serum albumin (Mr 65 000) which was used as a control. Kinetic competition studies between metallothionein and either a spin trap for .OH or ferricytochrome c for O-.2 radicals, gave bimolecular rate constants of the order of kOH/MT approximately equal to 10(12) M-1 X s-1 and kO-2/MT approximately equal to 5 X 10(5) M-1 X s-1, respectively. The former value suggests that all 20 cysteine sulfur atoms are involved in this quenching process and that they all act in the diffusion control limit. The aerobic radiolysis of an aqueous solution of metallothionein, generating O-.2 and .OH radicals, induced metal ion loss and thiolate oxidation. These effects could be reversed by incubation of the irradiated protein with reduced glutathione and the appropriate bivalent metal ion. Metallothionein appears to be an extraordinarily efficient .OH radical scavenger even when compared to proteins 10-50-times its molecular weight. Moreover, hydroxyl radical damage to metallothionein appears to occur at the metal-thiolate clusters, which may be repaired in the cell by reduced glutathione. Metallothionein has the characteristics of a sacrificial but renewable cellular target for .OH-mediated cellular damage.
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PMID:Possible role for metallothionein in protection against radiation-induced oxidative stress. Kinetics and mechanism of its reaction with superoxide and hydroxyl radicals. 298 55

Metallothionein inhibited in a concentration-dependent fashion the reduction of nitroblue tetrazolium [NBT] mediated by xanthine oxidase and by NADH-phenazine methosulfate. This catalytic activity of metallothionein for dismutation of O2- is dependent on the copper content in metallothionein.
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PMID:Inhibition of nitroblue tetrazolium reduction by metallothionein. 689 6

Metallothionein (MT) is a metal and thiol-rich protein readily induced by cadmium (Cd) exposure. In vitro experiments have demonstrated that MT is able to serve as a scavenger of hydroxyl radicals as well as superoxide anions, albeit to a lesser extent. The role of MT as a mediator in Cd induced oxidant resistance was investigated in a nontransformed human lung fibroblast cell line (IMR-90). Cells were passaged three times either in a Cd-containing medium (8.9 microM CdCl2) or in a medium which lacked Cd. Cellular MT content, as quantitated by a modification of the heme/109Cd binding assay, increased significantly with each passage in Cd. Immunocytochemistry studies revealed that all Cd-pretreated cells contained MT and that MT was localized in both cytoplasmic and nuclear compartments. Immunolabeling was more intense in some cells compared to others. Very slight immunolabeling was observed in physiological control cells, grown in the absence of Cd, and virtually no staining was observed in Cd-adapted or non-adapted cells when primary antibody was omitted. Using the xanthine/xanthine oxidase system as a generating system for active oxygen species, we found that the magnitude of cell injury for Cd-adapted and non-adapted fibroblasts was dependent upon oxidant concentration and duration of oxidant exposure. Cd-adapted fibroblasts, which were characterized by over-expression of MT, were significantly more resistant to injury by active oxygen species and also exhibited a greater ability to scavenge extracellular hydrogen peroxide compared to cells with no previous history of Cd exposure. Experiments with aminotriazole demonstrated that catalase was not a major contributor to the additional hydrogen peroxide scavenging capacity of Cd-adapted cells. The data presented in this report are consistent with involvement of MT in protecting critical cellular targets from reactive oxygen species.
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PMID:Oxidant resistance of cadmium-adapted human lung fibroblasts. 774 May 38

Based on the inhibition of nitrite formation by generating superoxide from xanthine/xanthine oxidase (X/XO) reaction system, metallothionein (MT) and other sulfhydryl containing amino acids have been selected to test their abilities to scavenge superoxide radicals. Different concentrations of metallothionein and other sulfhydryl containing molecules e.g. cysteine, N-acetyl-cysteine and glutathione, were used to assess superoxide scavenging properties. Metallothionein scavenges superoxide radical in a dose-dependent manner with increasing concentrations as evidenced by the inhibition of nitrite formation. Similar abilities to scavenge superoxide radicals were shown by cysteine, N-acetyl-cysteine. Glutathione also scavenges superoxide radical in a dose-dependent manner. In vitro experiments demonstrated that metallothionein is superior in scavenging superoxide radicals compared to other sulfhydryl molecules such as cysteine, N-acetyl-cysteine and even glutathione. The data, further, suggest that metallothionein-II has a 6-fold higher capacity to scavenge superoxide radical than metallothionein-I. In addition, metallothionein-like protein was isolated from different regions of mouse brain treated with zinc. Brain metallothionein-like protein inhibits nitrite formation as demonstrated by other scavengers; however, the extent of inhibition is different by this protein isolated from different brain regions. The present study suggests that metallothioneins and metallothionein-like proteins isolated from mouse brain act as neuroprotective agents by scavenging superoxide radicals.
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PMID:Role of metallothionein and other antioxidants in scavenging superoxide radicals and their possible role in neuroprotection. 883 43

Metallothionein (MT)-III is a member of a brain-specific MT family, in contrast to MT-I and MT-II that are found in most tissues and are implicated in metal ion homeostasis and as an antioxidant. To investigate the defensive role of MT-III in terms of hydroxyl radical-induced DNA damage, we used purified human MT-III. DNA damage was detected by single-strand breaks of plasmid DNA and deoxyribose degradation. In this study, we show that MT-III is able to protect against the DNA damage induced by ferric ion-nitrilotriacetic acid and H(2)O(2), and that this protective effect is inhibited by the alkylation of the sulfhydryl groups of MT-III by treatment with EDTA and N-ethylmaleimide. MT-III was also able to efficiently remove the superoxide anion, which was generated from the xanthine/xanthine oxidase system. These results strongly suggest that MT-III is involved in the protection of reactive oxygen species-induced DNA damage, probably via direct interaction with reactive oxygen species, and that MT-III acts as a neuroprotective agent.
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PMID:Protective effect of metallothionein-III on DNA damage in response to reactive oxygen species. 1238 39