Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mono-electronic reduction of oxygen in the hypoxanthine-xanthine oxidase system led to the formation of active species eliciting an evident and highly reproducible mutagenic response in strain TA104 of S. typhimurium. Similar effects were observed by generating oxy radicals either extracellularly or inside bacterial cells. Mutagenicity was selectively detected in TA104 and not in other Salmonella strains, which points out the importance of the hisG428 mutation and of the deletion excising the uvrB gene, as far as sensitivity to oxy radicals is concerned. The mutagenicity of the system was further enhanced in the presence of superoxide dismutase. Catalase did not affect the mutagenicity of hypoxanthine plus xanthine oxidase, whereas it inhibited the mutagenicity induced by the mixture of hypoxanthine with xanthine oxidase and superoxide dismutase. This demonstrates that not only hydrogen peroxide but also the superoxide radical anion is positive in this system. Glutathione and 2 synthetic thiols, i.e., N-acetylcysteine and alpha-mercaptopropionylglycine, besides decreasing the high spontaneous mutagenicity of TA104, efficiently prevented the mutagenicity of active oxygen species.
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PMID:Mutagenicity of active oxygen species in bacteria and its enzymatic or chemical inhibition. 267 96

Release of iron from ferritin by the polyhydroxypyrimidines, dialuric acid, isouramil, divicine, and acid-hydrolyzed vicine, was measured. Iron was released at fast initial rates which gradually declined to zero in 10 min. All the compounds were better reductants for ferritin-iron under nitrogen than in air. The effects of superoxide dismutase, catalase, and glutathione on both initial rates and total iron released over 30 min in air were determined. Major effects were inhibition by superoxide dismutase for divicine and isouramil and enhancement for dialuric acid and acid-hydrolyzed vicine. Glutathione promoted increased iron release that was further enhanced by superoxide dismutase. These increases were particularly striking over the longer time period. Catalase, in all cases, gave modest enhancement. Enhanced iron release correlated with inhibition of pyrimidine oxidation. The results indicate that the reduced form of each pyrimidine releases ferritin iron directly, and the effects of the antioxidants are mainly to maintain or regenerate the reduced pyrimidines. A combination of each pyrimidine and ferritin caused peroxidation of phopholipid liposomes, above that seen with the pyrimidines and adventitious iron. Glutathione, superoxide dismutase, and catalase modulated lipid peroxidation in a way consistent with their effects being mainly on ferritin-iron release. On the basis of our findings, we propose that the release and subsequent reactions of ferritin-iron may contribute to the toxicity of these compounds. Although glutathione and superoxide dismutase together efficiently inhibit redox cycling and H2O2 production from the pyrimidines, this combination maximized iron release from ferritin and ferritin-dependent lipid peroxidation.
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PMID:Release of iron from ferritin by divicine, isouramil, acid-hydrolyzed vicine, and dialuric acid and initiation of lipid peroxidation. 273 3

Hemin (ferric protoporphyrin IX chloride) in the presence of hydrogen peroxide or tert-butyl hydroperoxide was found to cleave folic acid at the C9-N10 bond. The ferrous form of hemin was not involved in hydroperoxide-dependent folic acid degradation, as indicated by the lack of inhibition by carbon monoxide. Molecular oxygen was not required for the degradation. GSH-Mn(II) or NAD(P)H in the presence of molecular oxygen did not support hemin-mediated folic acid degradation. The degradation increased as the temperature was elevated from 10 to 70 degrees C. Ascorbic acid and azide were potent inhibitors. Superoxide dismutase and hydroxyl radical quenchers, such as ethanol, mannitol, benzoate, and dimethyl sulfoxide did not inhibit the reaction. Catalase inhibited hydrogen peroxide-supported degradation but not the tert-butyl hydroperoxide-dependent one. Thiol compounds, such as thioglycolic acid, thiourea, glutathione, cysteine, and 2-mercaptoethanol, inhibited the hydrogen peroxide-dependent degradation but supported the tert-butyl hydroperoxide-mediated one. N5-formyl tetrahydrofolic acid, but not N10-formyl folic acid, was degraded by hemin in the presence of H2O2 or TBHP. The data obtained are suggestive of a mechanism similar to N-demethylation reactions catalyzed by cytochrome P-450 and some peroxidases.
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PMID:Studies on hydroperoxide-dependent folic acid degradation by hemin. 282 Mar 6

Evidence has been obtained that implicates the generation of reactive oxygen species as an early and critical event in the promotion of neoplastic transformation in mouse JB6 cells. The time courses for specific inhibition by CuZn-superoxide dismutase (CuZn-SOD) of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of neoplastic transformation in JB6 cells and for changes in antioxidant enzyme activities associated with TPA-exposure were examined. The antipromoting effect of CuZn-SOD was found to be critically dependent on the time of addition of CuZn-SOD relative to the start of a 14-day exposure of cells to TPA. Treatment of JB6 P+ Clone 22 and Clone 41 cells with CuZn-SOD for 18 h before, simultaneously with or up to 1 h after exposure to TPA, all inhibited promotion of transformation maximally. Delay of addition of CuZn-SOD by 2 h or more after the start of TPA treatment resulted in a marked decrease in the promotion inhibitory effect. CuZn-SOD added 24 or 48 h after TPA had no effect on promotion of transformation. Exposure of JB6 cells to 0.2- (superoxide anion radical) generated exogenously by the aerobic xanthine oxidase reaction resulted in promotion of neoplastic transformation that was prevented by concurrent addition of CuZn-SOD. Taken together these studies provide evidence that increased superoxide anion generation within the first 2 h following TPA exposure is an essential event in promotion of transformation in JB6 cells. Upon TPA exposure, JB6 Clone 41 cells exhibited time-specific activity changes in the cellular SOD, glutathione peroxidase (GSH-Px), and catalase. SOD and GSH-Px activities were reduced to 54% and 26% respectively of basal levels within 2 h of TPA treatment. GSH-Px activity recovered to basal levels within 4 h and CuZn-SOD within 48 h. Catalase activity was maximally reduced to 50% of basal within 1 h after TPA treatment and rebounded to greater than basal levels within 4 h. It is postulated that a c-kinase-dependent event induces rapid elevation of superoxide anion following TPA exposure and that this leads to reduced activity of antioxidant enzymes. Since antipromotion by exogenous CuZn-SOD is effective only during the first 2 h following TPA exposure, this suggests that the promotion-relevant 0.2- elevation is transient.
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PMID:Early superoxide dismutase-sensitive event promotes neoplastic transformation in mouse epidermal JB6 cells. 282 3

The present findings provide experimental evidence for the hypothesis that compromised cellular defense mechanisms, i.e., glutathione (GSH), GSH-peroxidase and catalase in the brain may be involved in neuronal degeneration caused by manganese (Mn) neurotoxicity. Moreover, data are presented demonstrating that the striatum is particularly susceptible to the deleterious effects of Mn. Specifically, exposure to subchronic MnCl2 produced significant reductions in GSH-peroxidase activity in the cytosol and mitochondrial fractions of the whole brain and the striatum. The decrease in GSH-peroxidase was most pronounced in the mitochondrial fraction of the striatum where the activity was reduced to 35% of the control. Catalase activity was also decreased in the striatum of rats treated with Mn but not in the whole brain. GSH content was markedly depleted (20% of the control) in the striatum, although only modestly decreased in whole brain (80% of the control). The alterations in the above parameters were accompanied by depletion of dopamine and dopamine metabolites in the striatum. The treatment of rats with Mn also decreased the activity of oxidized glutathione-reductase; the same treatment increased the activity of gamma-glutamyltranspeptidase. The activity of gamma-glutamylcysteine synthetase was not altered by Mn. The possible relevancy of the findings of this study to understanding the mechanism of Mn neurotoxicity of dopamine systems is discussed.
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PMID:Selective vulnerability of glutathione metabolism and cellular defense mechanisms in rat striatum to manganese. 290 11

The interaction of reduced glutathione (GSH) with active oxygen species generated during xanthine-oxidase-catalyzed metabolism of xanthine was investigated. The only GSH-derived product detected in this system was oxidized glutathione (GSSG). Catalase inhibited the oxidation of GSH to GSSG by more than 80%, whereas superoxide dismutase exerted a smaller but significant inhibition of GSSG formation. Hydroxyl radical (OH) scavengers or desferrioxamine (1 mM) had no effect on GSSG formation. Using EPR spectroscopy and the spin trap 5,5-dimethylpyrroline-N-oxide (DMPO), the production of superoxide was observed by the detection of a DMPO-OOH radical adduct. This spectrum was altered by the inclusion of GSH (5 - 20 mM) in the reaction mixture, indicating the generation of a different radical species consistent with DMPO-glutathionyl radical adduct generation.
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PMID:The interaction of reduced glutathione with active oxygen species generated by xanthine-oxidase-catalyzed metabolism of xanthine. 299 2

The interaction of menadione with reduced glutathione (GSH) led to a removal of menadione and formation of menadione-GSH conjugate and glutathione disulfide (GSSG). The changes in thiol level were essentially biphasic with an initial rapid decrease in GSH and appearance of GSSG (less than 1 min) followed by secondary less pronounced changes. The interaction of menadione and GSH caused an oxygen uptake and both superoxide anion radical and hydrogen peroxide were produced during the reaction, the amount dependent on the GSH/menadione ratio. Catalase did not protect against the initial decrease in GSH level but markedly inhibited the secondary changes while superoxide dismutase had little effect. These results suggest that the initial changes in thiol level are the result in part of a redox reaction between menadione and GSH as well as conjugate formation, whilst the secondary changes reflect conjugate formation and the activity of other oxidants such as hydrogen peroxide. The potential biological significance of this reaction was investigated using hepatocytes depleted of reduced pyridine nucleotides and thus not able to perform enzyme-catalyzed reduction of menadione. In these cells menadione induced GSSG formation at a rate similar to that observed in control cells. This suggests that quinone-induced oxidative challenge caused by the chemical interactions of a quinone and glutathione may have biological relevance.
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PMID:Interaction of menadione (2-methyl-1,4-naphthoquinone) with glutathione. 299 31

Photoemissive excited species are produced by the horseradish peroxidase (HRP)-catalyzed oxidation of reduced glutathione (GSH), without exogenously added hydroperoxide under aerobic conditions. The emitted low-level chemiluminescence consisted of two phases. Light emission occurred at wavelengths beyond 610 nm (greater than or equal to 90% intensity), indicative of singlet oxygen 1O2. Deuterium oxide enhanced photoemission 4.4-fold. Ascorbate inhibited chemiluminescence completely. In the absence of GSH or when GSH was replaced by the disulfide, no red chemiluminescence was observed. The glutathionyl radical GS. is most likely to be involved in both phases of light emission. Further, the superoxide radical plays a role, as substantiated by the inhibitory effect of superoxide dismutase. Both phases of photoemission were abolished by glutathione peroxidase; thus hydroperoxides are regarded as essential intermediates for the formation of excited species. Catalase abolished phase I and did not affect phase II. In contrast, glutathione S-transferase 1-2 (showing peroxidase activity towards organic hydroperoxides but not towards H2O2) inhibited phase II, whereas phase I was still present. Glutathione sulfonate and the disulfide GSSG were detected as oxidation products from GSH under conditions where phase II chemiluminescence was observed. HRP Compound III accumulated during the reaction. It is concluded that phase I is dependent on exogenously added or endogenously generated H2O2, whereas phase II does not require H2O2 but an organic peroxy species. A mechanism based on chain reactions involving oxygen addition to the thiyl radical is proposed. Sulfenyl peroxy species are suggested as transient intermediates in reactions finally leading to the generation of excited states such as singlet molecular oxygen.
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PMID:Excited species generation in horseradish peroxidase-mediated oxidation of glutathione. 301 81

Catalase (CAT), glutathione-peroxidase (GSH-Px) activity and reduced glutathione content (GSH) were measured in patients who had hepatocellular carcinoma, and values compared with those of normal liver and liver adjacent to neoplastic tissue. The results showed a remarkable reduction of CAT in tumor and corresponding tumor-free tissue (P less than 0.001 and P less than 0.02, respectively). All neoplastic samples had a significant lower activity of CAT than the corresponding adjacent tumor-free tissue (P less than 0.05). The GSH-Px activity of tumor tissue also was lower than normal (P less than 0.001) but similar to that of adjacent tissue. No correlation was noted between the two enzyme activities. Glutathione content was extremely low in tumor (P less than 0.001) and even in tumor-free tissue (P less than 0.05) when compared with normal liver. In all cases the content of GSH in neoplastic tissue was lower than that of the corresponding tumor-free tissue (P less than 0.05). Whereas in normal liver the activity of GSH-Px was positively correlated with the content of GSH, in the neoplastic tissue such a relationship disappeared. All these findings suggest that the antioxidant system of hepatocellular carcinoma cell is severely impaired.
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PMID:Severe impairment of antioxidant system in human hepatoma. 301 7

The mechanism of cytogenetic genotoxicity (clastogenicity, induction, cell cycle delay) of 10(-3) M glutathione in V79-E cells, as described by Thust and Bach (1985), was studied in detail by using different treatment conditions. It was found that 1-cystine is the essential cofactor in the incubation system. Catalase, but not superoxide dismutase, abolished the genotoxic effect, and the iron chelator desferoxamine, as well as the hydroxyl radical scavenger mannitol, diminished the activity. It is suggested that glutathione, in combination with V79-E cells and cystine, forms a hydrogen peroxide-generating system which provokes the adverse effects. Glutathione as well as 1-cysteine and 2-mercaptopropionylglycine, which were checked for comparison, show a "paradoxic genotoxicity," i.e., at 10(-2) M the effects return almost to the level of controls. Concentration dependence and other criteria of cytogenetic genotoxicity observed with glutathione show obvious similarities to those of other oxidatively acting agents and reveal striking differences to the cytogenetic effects of "typical" genotoxins.
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PMID:The mechanism of cytogenetic genotoxicity of exogenous glutathione in V-79 cells in vitro--implication of hydrogen peroxide and general traits of oxidative chromosome damage. 323 33


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