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)

Endogenous hydrogen peroxide (H2O2) release from aortic endothelial cells was studied in the presence of antioxidant enzyme inhibitors, mitochondrial inhibitors, a microsomal cytochrome P-450 inhibitor, and after oxidative stress induced with H2O2 or menadione. Extracellular H2O2 generation was determined spectrofluorometrically using 3-methoxy-4-hydroxy phenylacetic acid, and intracellular H2O2 production (in or near peroxisomes) was measured indirectly using aminotriazole, which inactivates catalase in the presence of H2O2. Extracellular H2O2 release was 0.079 +/- 0.005 nmol/min/mg protein in Hanks' balanced salt solution, was constant during a 120-min incubation period, and was not affected by the cell passage number. The half-life for catalase inactivation with aminotriazole was 23 min. Inhibition of catalase, glutathione reductase, or gamma-glutamylcysteine synthetase did not change the rate of extracellular release of H2O2. Furthermore, inhibition of the mitochondrial respiratory chain (rotenone, antimycin A) or microsomal cytochrome P-450 (8-methoxypsoralen) did not change extracellular H2O2 release or intracellular H2O2 production (at peroxisomes) by endothelial cells or cells in which glutathione reductase was inactivated. When the cells were exposed to exogenous H2O2 (30 microM), extracellular H2O2 was scavenged primarily by the glutathione redox pathway. Exogenously added H2O2 (100 microM) changed intracellular H2O2 production (in or near peroxisomes) only when the glutathione redox cycle was inactivated. Menadione (20 microM), which undergoes intracellular redox cycling, increased extracellular H2O2 release almost 4-fold to 0.3 nmol/min/mg protein. Furthermore, menadione increased peroxisomal H2O2 levels and decreased the half-life for catalase inactivation in the presence of aminotriazole to 13 min. Catalase inhibition increased extracellular H2O2 release during menadione treatment, indicating that H2O2 can diffuse across the plasma membrane during oxidant stress.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of hydrogen peroxide generation in cultured endothelial cells. 154 Mar 80

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

To investigate oxidative effects of N-nitrosodimethylamine (NDMA) on the liver, rats were challenged by the reagent with a dose range of 10 to 40 mg/kg. With lower dose levels, protective responses were prominent, such as elevation of the hepatic glutathione and metallothionein (MT) levels. Increased activities were also evident of gamma-glutamylcysteine synthetase, glucose-6-phosphate dehydrogenase (G6PD), and malic enzyme. In the high dose range, however, toxic responses, such as increases in lipid peroxide levels in liver and serum, and glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), and ketone bodies in serum became marked. Some of the protective responses became less marked at the highest dose. Catalase and glutathione peroxidase activities in the liver were also inhibited by NDMA treatment. On the other hand, when NDMA was injected as a series of doses (10 mg/kg on four separate occasions), the effects were less marked, and the hepatic levels of MT and lipid peroxide remained unchanged even after the 4th injection. Only the increase in G6PD activity was more marked after four times repeated injection than after a single injection. These results suggest that oxidative and hepatotoxic effects of NDMA are more moderate when given in repeated doses than in a single dose. In contrast to the liver, elevation of MT levels was the only detectable change in the kidney.
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PMID:Effects of N-nitrosodimethylamine (NDMA) on the oxidative status of rat liver. 1040 79