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 ability of aurothioglucose and D(-)-penicillamine hydrochloride to inhibit selenium-dependent glutathione peroxidase (SeGSH-Px) in vitro and to increase exudative diathesis in vitamin E-deficient chickens was studied. Aurothioglucose and penicillamine competitively inhibited SeGSH-Px in inverse proportion to the concentration of hydrogen peroxide and reduced glutathione, respectively, in chick liver postmitochondrial supernatant assay preparations. Neither drug inhibited glutathione reductase or superoxide dismutase at the concentrations tested; however, both inhibited catalase in a semilogarithmic fashion. This was true for both the purified bovine enzyme and chick liver homogenate. Aurothioglucose and penicillamine injected subcutaneously at the back of the neck increased exudative diathesis in vitamin E-deficient chickens fed 0.1 ppm Se, and effectively overcame the protective effect of selenium 72 h after injection in chicks fed vitamin E-free, low selenium diets supplemented with 0.0-0.1 ppm Se. Assays of plasma and of liver, lung and kidney postmitochondrial supernatants indicated that all observed reductions in SeGSH-Px activity preceded increases in exudative diathesis. Plasma and liver SeGSH-Px activities were lower at early times (6-24 h) after treatment with high doses of either drug. Lung SeGSH-Px activities were only lower in chicks receiving 240 mg penicillamine/kg 6 h after treatment; kidney SeGSH-Px activities were only lower in chicks treated with the highest dose of aurothioglucose 48 h after treatment. Brain SeGSH-Px activities were unaffected by drug treatment and the heart had higher SeGSH-Px activities only at 6 h after treatment with the highest dose of either drug compared to saline controls. Catalase activities in liver homogenates were only significantly altered by penicillamine; the highest dose caused the activity to be higher than that in saline-treated chicks. The cause of the lower SeGSH-Px activities could be either lower enzyme concentrations in tissues of the drug-treated groups and/or direct inhibition. Whatever the mechanism, it is concluded that exudative diathesis can be used to determine which drugs reduce SeGSH-Px activity in the chick.
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PMID:Drug-induced changes in selenium-dependent glutathione peroxidase activity in the chick. 393 15

The catalase activity of cultured rat hepatocytes was inhibited by 90% pretreatment with 20 mM aminotriazole without effect on the activities of glutathione peroxidase or glutathione reductase, or on the viability of the cells over the subsequent 24 h. Glutathione reductase was inhibited by 85% by pretreatment with 300 microM 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) without effect on glutathione peroxidase, catalase, or on viability. Both pretreatments sensitized the hepatocytes to the cytotoxicity of H2O2 generated either by glucose oxidase (0.05-0.5 units/ml) or by the autoxidation of the one-electron-reduced state of menadione (50-250 microM). Aminotriazole pretreatment had no effect on the GSH content of the hepatocytes. BCNU reduced GSH levels by 50%. Depletion of GSH levels to less than 20% of control by treatment with diethyl maleate, however, did not sensitize the cells to either glucose oxidase or menadione, indicating that the effect of BCNU is related to inhibition of the GSH-GSSG redox cycle rather than to the depletion of GSH. With glucose oxidase, most of the cell killing in hepatocytes pretreated with either aminotriazole or BCNU occurred between 1 and 3 h. The antioxidant diphenylphenylenediamine (DPPD) had no effect on viability at 3 h. Catalase added to the culture medium 1 h after the addition of glucose oxidase prevented the cell killing measured at 3 h. The sulfhydryl reagents dithiothreitol (200 microM), N-acetyl-L-cysteine (4 mM), and alpha-mercaptopropionyl-L-glycine (2.5 mM) prevented the cell killing with exogenous H2O2 in hepatocytes sensitized by the inhibition of catalase or glutathione reductase. With menadione, there was no killing of nonpretreated hepatocytes at 1 h, and DPPD did not prevent the cell death after 3 h. Aminotriazole pretreatment enhanced the cell killing at 3 h but not at 1 h, and DPPD was not protective. Catalase added to the medium at 1 h inhibited the cell death measured at 3 h. In contrast, menadione killed hepatocytes pretreated with BCNU within 1 h. DPPD prevented cell death at 1 h, and there was evidence of lipid peroxidation in the accumulation of malondialdehyde in the culture medium. Catalase added with menadione did not prevent the cell killing at 1 h but did prevent it at 3 h. These data indicate that catalase and the GSH-GSSG cycle are active in the defense of hepatocytes against the toxicity of H2O2.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endogenous defenses against the cytotoxicity of hydrogen peroxide in cultured rat hepatocytes. 396 66

The nature of the aging process has been the subject of considerable speculation. Now, some data indicate that free radical reactions going on continuously in the cells contribute to aging. Considering these data, we have investigated the activity of enzymes (catalase, glutathione peroxidase, superoxidismutase) present physiologically in the cell to limit to tolerable levels, the rate of free radicals or H2O2. These enzymes activities were assayed in Paramecium tetraurelia as clonal age increased. Catalase activity increases slightly during aging of paramecia, i.e. during maturity and senescence phases (20-150 fissions). No significant changes in glutathione peroxidase and superoxidismutase is found. Catalase activity was also assayed as a function of culture conditions. As the cells begin starving and the percentage of autogamous cells increases, catalase activity decreases. After autogamy, a large increase of catalase activity occurs during the sexual immaturity phase, i.e. during the first 20 fissions. By another way, H2O2 added in the culture medium (from 0 to 15 X 10(-5)M) causes an important increase of catalase activity (from 100 U.I. to 250 U.I.). The possible role of O-.2, OH. and H2O2 in aging is discussed.
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PMID:Studies on catalase, glutathione peroxidase and superoxidismutase activities in aging cells of Paramecium tetraurelia. 398 82

A significant inactivation of red blood cell glutathione peroxidase (25% less than the physiological value) was observed after exposure of intact erythrocytes to 2 mM divicine (an autoxidizable aminophenol from Vicia faba seeds) and 2 mM ascorbate for 3 h at 37 degrees C. Addition of catalase and conversion of Hb to the carbomonoxy derivative resulted in protection against enzyme inactivation. Oxidation of Hb was a concurrent phenomenon, and augmented the inactivating effect. In hemolysates, much stronger effects were observed at shorter times (2 h); divicine was effective also without ascorbate, and the presence of reductants (ascorbate or glutathione or NADPH) enhanced its inactivating power. Of the other antioxidant enzymes, superoxide dismutase was unaffected under the same experimental conditions. Catalase was found to be much less sensitive to the inactivation; it was almost unaffected in experiments with intact erythrocytes and specifically protected by NADPH in experiments with hemolysates. This specific damage of glutathione peroxidase, apparently involving interaction of H2O2 and HbO2, may be related to the pathogenesis of hemolysis in favism.
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PMID:Inactivation of red cell glutathione peroxidase by divicine and its relation to the hemolysis of favism. 406

Current evidence suggests that bleomycin toxicity may be attributable to its DNA degradative activity possibly via generation of free radicals and O2 metabolites as mediators. Since lipopolysaccharide (LPS) has been known to provide protection against O2 toxicity, which is correlated with increased activity of O2 metabolite-detoxifying enzymes, the effect of this agent on bleomycin-induced pulmonary fibrosis was examined. Endotracheal bleomycin administration caused increased lung collagen synthesis. A single intraperitoneal injection of LPS (500 micrograms/kg) at day zero significantly decreased these increases. Total bleomycin-induced lung collagen increase was also significantly reduced. LPS alone had no significant effect on total lung catalase activity. Glutathiione peroxidase activity, however, was significantly decreased by 15.8% compared to untreated animals at 2 days after LPS treatment and remained unchanged at other time points. In addition, superoxide dismutase activity was significantly elevated by 30% above untreated animals only at 14 days after LPS administration and remained unchanged at other time points. Endotracheal bleomycin administration alone caused significant reductions in catalase activity at 2 days and 2 weeks after treatment, whereas glutathione peroxidase activity increased above control untreated animals at 2 and 4 weeks, respectively. Superoxide dismutase activity was unaffected by bleomycin treatment. Pretreatment with LPS before bleomycin prevented these reductions or caused increases in the activities of these enzymes at 2 days. Glutathione peroxidase was increased and was significantly greater than those animals treated with bleomycin alone. Catalase also was higher in the LPS plus bleomycin group (by 22.2%, p less than 0.05) than the bleomycin group alone. Compared to the effects on lung collagen synthesis and content, LPS treatment resulted in much less dramatic changes in total lung antioxidant enzyme activities. This discrepancy between the intensity of LPS effects on lung O2 metabolite-detoxifying enzymes and that on pulmonary fibrosis implies that the LPS-ameliorating effect on pulmonary fibrosis could not be totally explained by increased ability to detoxify O2 metabolites. Rather, the data would favor the possibility that LPS inhibits bleomycin-induced pulmonary fibrosis either by its known immunosuppressive effects or some other unknown mechanism. The former would be in agreement with previous data which suggest that an intact immune response is necessary for complete expression of the fibrogenic response to bleomycin.
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PMID:Inhibition of bleomycin-induced pulmonary fibrosis by lipopolysaccharide. 620 76

The synthesis of glutathione peroxidase from [75Se]selenite was studied in slices and cell-free extracts from rat liver. The incorporation of [75Se]selenocysteine at the active site was detected by carboxymethylation and hydrolysis of partially purified glutathione peroxidase (glutathione:hydrogen peroxide oxidoreductase, EC 1.11.1.9) in the presence of [3H]selenocysteine and subsequent amino acid analysis. The synthesis of glutathione peroxidase in slices was inhibited by cycloheximide or puromycin and 75Se was incorporated from [75Se]selenite into free selenocysteine and selenocysteyl tRNA. Increasing concentrations of selenocystine caused a progressive dilution of the 75Se and a corresponding decrease in glutathione peroxidase labeling. In cell-free systems, [75Se]selenocysteyl tRNA was the best substrate for glutathione peroxidase synthesis. These results indicate the existence in rat liver of the de novo synthesis of free selenocysteine and a translational pathway of selenocysteine incorporation into glutathione peroxidase.
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PMID:In vitro synthesis of glutathione peroxidase from selenite. Translational incorporation of selenocysteine. 621 28

This investigation examined the effect of the anthracycline antitumor agents on reactive oxygen metabolism in rat heart. Oxygen radical production by doxorubicin, daunorubicin, and various anthracycline analogues was determined in heart homogenate, sarcoplasmic reticulum, mitochondria, and cytosol, the major sites of cardiac damage by the anthracycline drugs. Superoxide production in heart sarcosomes was significantly increased by anthracycline treatment; for doxorubicin, the reaction appeared to follow saturation kinetics with an apparent Km of 112.62 microM, required NADPH as cofactor, was accompanied by the accumulation of hydrogen peroxide, and probably resulted from the transfer of electrons to molecular oxygen by the doxorubicin semiquinone after reduction of the drug by sarcosomal NADPH:cytochrome P-450 reductase (NADPH:ferricytochrome oxidoreductase, EC 1.6.2.4). Superoxide formation was also significantly enhanced by the anthracycline antibiotics in the mitochondrial fraction. Doxorubicin stimulated mitochondrial superoxide formation in a dose-dependent manner that also appeared to follow saturation kinetics (apparent Km of 454.55 microM); however, drug-related superoxide production by mitochondria required NADH rather than NADPH and was significantly increased in the presence of rotenone, which suggested that the proximal portion of the mitochondrial NADH dehydrogenase complex [NADH:(acceptor) oxidoreductase, EC 1.6.99.3] was responsible for the reduction of doxorubicin at this site. In heart cytosol, anthracycline-induced superoxide formation and oxygen consumption required NADH and were significantly reduced by allopurinol, a potent inhibitor of xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.2.3.2). Reactive oxygen production was detected in all of our studies despite the presence of both superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) and glutathione peroxidase (glutathione:hydrogen peroxide oxidoreductase, EC 1.11.1.9) in each cardiac fraction. These results suggest that free radical formation by the anthracycline antitumor agents, which occurs in the same myocardial compartments that are subject to drug-induced tissue injury, may damage the heart by exceeding the oxygen radical detoxifying capacity of cardiac mitochondria and sarcoplasmic reticulum.
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PMID:Effect of anthracycline antibiotics on oxygen radical formation in rat heart. 629 97

This study investigated the effect (in vivo) of centrophenoxine (Helfergin) on the activity of antioxidant enzymes (glutathione peroxidase GSH-PER, glutathione reductase GSSG-RED, superoxide dismutase SOD and catalase) in subcellular fractions from the regions of the brain (cerebrum, cerebellum and brain stem) of rats aged 6, 9 and 12 months. In all age groups, normal (control) activity of GSH-PER, GSSG-RED and SOD in the three brain regions was higher in the soluble fractions than in the particulate fractions. The three regions of the brain showed different levels of the enzyme activities. Enzymes in soluble fractions (except GSSG-RED in cerebrum of rats aged 12 months) did not change with age. In particulate fractions, however, the enzymes showed age-related changes: GSH-PER decreased with age in cerebellum and brain stem, but showed an age-related increase in cerebrum, GSSG-RED and SOD increased with age in all the three brain regions. Catalase activity in all the three brain regions remained unchanged in all age groups. Six week administration of centrophenoxine (once a day in doses of 80 mg/Kg and 120 mg/Kg) to the experimental animals produced increases in the activity of SOD, GSH-PER and GSSG-RED in particulate fractions from all the three brain regions. In the soluble fractions, however, only SOD and GSH-PER activity was increased. In vitro also centrophenoxine stimulated the activity of GSH-PER. A dosage of 80 mg/Kg produced greater changes than a 120 mg/Kg dosage. The drug had no effect on the activity of catalase. Centrophenoxine also reduced lipofuscin deposits (studied both biochemically and histochemically) thus indicating that the drug inhibited lipofuscin accumulation by elevating the activity of the antioxidant enzymes. The data suggest that alleviation of senescence by centrophenoxine may, at least, partly be due to activation by it of antioxidant enzymes.
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PMID:Effect of centrophenoxine on the antioxidative enzymes in various regions of the aging rat brain. 641 80

The trace element selenium is known to be a part of the enzyme glutathione peroxidase (glutathione-hydrogen peroxide oxidoreductase, E.C.1.11.1.9). Studies have shown that selenium in the enzyme exists in at least two forms or oxidation states. It is probable that selenium has been incorporated into the enzyme as the selenocysteine amino acid. In the present study, the Raman spectra of selenocystine and selenomethionine have been obtained, structural assignments have been verified, and the behavior of the two selenoamino acids have been monitored under varying conditions of oxidative stress. The assignments will assist in the interpretation of the spectrum of the actual enzyme.
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PMID:The Raman spectra of selenomethionine and selenocystine. 645 62

In cells the level of potentially toxic superoxide radical (O2-) is controlled by superoxide dismutase (SOD); the level of hydrogen peroxide (H2O2), also potentially toxic, is controlled by catalase and glutathione peroxidase. To study the effects of altered food intake or dietary protein content on SOD and catalase in cardiac and skeletal muscles, young rats were fed ad libitum diets containing 3, 6 or 25% casein or were subjected to total or partial food restriction (resulting in similar body weight losses). Rats fed a diet containing 3 or 6% casein had much lower growth rates than those fed 25% casein, but the muscle catalase activities were similar in all three groups. Catalase activities in muscles of rats whose food intake was restricted were twice those in rats fed ad libitum. Rats fed ad libitum had higher muscle SOD activities at 41 days of age than did 25-day-old rats, irrespective of the amount of dietary protein or the rate of growth. Twenty-five-day-old rats whose food intake was totally restricted for 2 days had skeletal muscle SOD activities similar to the higher activities seen at 41 days of age in ad libitum-fed rats, but SOD activity in the heart was unchanged after food restriction. The responses of catalase and SOD in muscles differ from the responses reported for these enzymes in liver and erythrocytes when food intake or dietary protein is altered.
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PMID:Effect of level of dietary protein and total or partial starvation on catalase and superoxide dismutase activity in cardiac and skeletal muscles in young rats. 650 67


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