Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GSH, GSSG, vitamin E, and ascorbate were measured in 14-day cultures of chick astrocytes and neurons and compared with levels in the forebrains of chick embryos of comparable age. Activities of enzymes involved in GSH metabolism were also measured. These included gamma-glutamylcysteine synthetase, GSH synthetase, gamma-glutamyl cyclotransferase, gamma-glutamyltranspeptidase, glutathione transferase (GST), GSH peroxidase, and GSSG reductase. The concentration of lipid-soluble vitamin E in the cultured neurons was found to be comparable with that in the forebrain. On the other hand, the concentration of vitamin E in the astrocytes was significantly greater in the cultured astrocytes than in the neurons, suggesting that the astrocytes are able to accumulate exogenous vitamin E more extensively than neurons. The concentrations of major fatty acids were higher in the cell membranes of cultured neurons than those in the astrocytes. Ascorbate was not detected in cultured cells although the chick forebrains contained appreciable levels of this antioxidant. GSH, total glutathione (i.e., GSH and GSSG), and GST activity were much higher in cultured astrocytes than in neurons. gamma-Glutamylcysteine synthetase activity was higher in the cultured astrocytes than in the cultured neurons. GSH reductase and GSH peroxidase activities were roughly comparable in cultured astrocytes and neurons. The high levels of GSH and GST in cultured astrocytes appears to reflect the situation in vivo. The data suggest that astrocytes are resistant to reactive oxygen species (and potentially toxic xenobiotics) and may play a protective role in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vitamin E, ascorbate, glutathione, glutathione disulfide, and enzymes of glutathione metabolism in cultures of chick astrocytes and neurons: evidence that astrocytes play an important role in antioxidative processes in the brain. 790 54

The activities of enzymes related to glutathione synthesis, degradation, and function were analyzed in various brain regions (cerebral cortex, caudate nucleus, putamen, globus pallidus, and substantia nigra) from patients dying with pathologically proven Parkinson's disease (PD) and multiple system atrophy (MSA), and from matched controls with no neurological disorder. The activity of the glutathione degradative enzyme, gamma-glutamyltranspeptidase, was selectively elevated in substantia nigra (SN) in PD. In contrast, the activity of the synthetic enzyme, gamma-glutamylcysteine synthetase, was unaltered in SN and other brain areas in PD. Similarly, glutathione peroxidase and glutathione transferase activities were unaltered in SN or in other brain regions in PD. gamma-Glutamylcysteine synthetase, gamma-glutamyltranspeptidase, glutathione peroxidase, and glutathione transferase activities were normal in SN and most other brain areas in MSA. However, glutathione peroxidase activity was increased in the lateral globus pallidus and caudate nucleus in MSA. The depletion of reduced glutathione (GSH) in the SN in PD, with no change in oxidized glutathione (GSSG), may be due to efflux of GSH mainly out of glia promoted by gamma-glutamyltranspeptidase, perhaps with additional increased conversion of GSH to GSSG (which itself is transported out of cells by gamma-glutamyltranspeptidase), in response to increased hydrogen peroxide formation.
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PMID:Glutathione-related enzymes in brain in Parkinson's disease. 808 Feb 39

gamma-Glutamylcysteine synthetase (gamma-GCS) is a rate-limiting enzyme in the de novo synthesis of glutathione, a known scavenger of electrophiles and reactive oxygen species (ROS). The gamma-GCS gene is expressed ubiquitously and induced coordinately with NAD(P)H:quinone oxidoreductase(1) (NQO1) and glutathione S-transferase Ya (GST Ya) in response to xenobiotics and antioxidants. The antioxidant response element (ARE) is required for expression and induction of these genes. In the current report, we demonstrated that ARE-mediated gamma-GCS gene expression and induction is regulated by similar Nrf and Jun factors as reported earlier for the NQO1 and GST Ya genes. The gamma-GCS gene ARE competed with the binding of nuclear proteins (Nrf + Jun) to the NQO1 gene ARE (hARE). In addition, the overexpression of Nrf2 and Nrf1 with c-Jun significantly up-regulated gamma-GCS ARE-mediated basal expression and beta-naphthoflavone induction of the chloramphenicol acetyltransferase gene in transfected HepG2 cells. Interestingly, Nrf2 + c-Jun was more effective than Nrf1 + c-Jun in the regulation of ARE-mediated gamma-GCS gene expression. Further experiments demonstrated that the c-Jun level within the cells is an important determinant of the level of ARE-mediated gamma-GCS gene expression. Therefore, at higher concentrations of c-Jun, gamma-GCS gene expression is repressed, presumably due to generation of a sufficient amount of c-Jun + c-Fos complex that interferes with the binding of Nrf2 + c-Jun complex to the ARE.
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PMID:Nrf2 and c-Jun regulation of antioxidant response element (ARE)-mediated expression and induction of gamma-glutamylcysteine synthetase heavy subunit gene. 1075 53

The present study examines the effects of thiabendazole (TBZ), its metabolites, 5-hydroxythiabendazole (5-OH TBZ) and 2-acetylbenzimidazole (ABI), and structural related compounds, thiazoles and thioamides on glutathione (GSH) concentration and GSH-related enzymes in the livers of ICR 11 week-old female mice. GSH concentration in liver and kidney of mice given orally TBZ 0.65 mol/kg (TBZ group) increased significantly compared with control mice from 24 h to 48 h after administration of TBZ. Even in mice to which TBZ at 0.175 mol/kg was administered in combination with L-buthionine sulfoximine (BSO) 4 mmol/kg (i.p.) (BSO-TBZ group), kidney GSH showed significant increase compared with BSO-control mice 48 h after the administration of TBZ. gamma-Glutamylcysteine synthetase (gamma-GCS) activity in the livers of the TBZ group markedly increased at 48 h and that of BSO-TBZ group increased from 24 h to 48 h. gamma-GCS in mice liver is thus enhanced by TBZ regardless of BSO administration. Hepatic glutathione peroxidase activity of the TBZ group did not change in response to cumene hydroperoxide assubstrate. That of BSO-treated mice decreased by TBZ-coadministration and significant differences was noted between BSO-control and BSO-TBZ group from 1 h to 48 h later. Hepatic glutathione S-transferase (GST) activity toward 1,2-dichloro-4-nitrobenzene (DCNB) was significantly elevated 24 h after administrations of TBZ in TBZ and BSO-TBZ groups. GST activity toward 1,2-epoxy-3-(p-nitrophenoxy) propane of TBZ group increased from 0.5 h to 24 h. Hepatic GST activity toward DCNB and 1-chloro-2,4-dinitrobenzene did not change by administration of 0.65 mol/kg 5-OH TBZ or ABI but increased by administrations of 0.33 mol/kg of thiazole, 4-methylthiazole, 4,5-dimethylthiazole or 2,4-dimethylthiazole. Increase in GSH concentration and GST activity in mice liver by TBZ administration may be considered to provide protection from TBZ or its active metabolites.
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PMID:[Effect of thiabendazole (TBZ) on glutathione (GSH) and GSH related enzymes in mice liver]. 1101 51

Cellular defense system, including glutathione, glutathione-related enzymes, and antioxidant and redox enzymes, may play crucial roles in the aging of aerobic organisms. To understand the physiological roles of these factors in the aging process, their levels were compared in the livers and brains of 5-week- and 9-month-old rats. GST activity was higher in livers and brains of 9-month-old rats than in those of 5-week-old rats, and brain catalase activity was about 2-fold higher. However, it was unchanged in the livers of the 9-month-old rats. gamma-Glutamylcysteine synthetase activity was about 2-fold higher in the brains of the older rats but again not in their livers. In contrast glutathione synthetase activity appeared to be lower in the livers of the older rats while GSH content did not change with age in livers and brains. Glutathione peroxidase activity was higher in 9-month-old rat brains, but lower in 9-month-old rat livers, while superoxide dismutase activity was higher in both tissues in the older rats. The activities of two redox enzymes, thiol-transferase and thioredoxin reductase, did not change with age, nor did that of glutathione reductase. These results indicate that levels of different cellular defense systems vary with age in an irregular manner.
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PMID:Age-related changes in the activity of antioxidant and redox enzymes in rats. 1474 15