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)

A recent finding in epidemiological and laboratory studies suggests that the ratio of selenium to glutathione is lower in breast cancer subjects than its control counterparts. Selenium, an antioxidant and anticarcinogen, can modify the status of glutathione and some associated enzymes by blocking peroxidation of lipids in membranes of cancer subjects. Studies were conducted using female albino rats of Wistar strain bearing mammary tumor induced by 7,12-dimethylbenz(a) anthracene to assess the biological role of selenium on some antioxidant enzymes associated with the maintenance of glutathione status. For induction of mammary tumor, 25 mg DMBA in a 1 ml emulsion of sunflower oil and physiological saline was injected subcutaneously to each rat. One group in each of control and tumor bearing rats, were fed 5 mg sodium selenite/kg diet from the day of tumor induction for 24 weeks. Increase in the reduced glutathione concentration was preceded by significant increase in the oxidized glutathione as well as in the activities of gamma-glutamylcysteine synthetase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, and glucose-6-phosphate dehydrogenase by selenium administration in rats bearing tumor. However, selenium administration to rats bearing tumor decreased the activity of gamma-glutamyl transpeptidase. These observations clearly demonstrate the influence of dietary selenium supplementation in correcting abnormal changes in glutathione turnover and some associated enzymes in tumor induced rats.
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PMID:Influence of selenium on glutathione and some associated enzymes in rats with mammary tumor induced by 7,12-dimethylbenz(a)anthracene. 909 65

Hydroxylamine (HYAM, HONH2) and some of its derivatives are known to cause erythrotoxic effects both in vitro and in vivo. Previous studies have shown that the primary in vitro effect of HYAM and O-ethyl hydroxylamine (OEH) is methaemoglobin formation, leading to liberation of free radicals which cause lipid peroxidation, enzyme inhibitions and glutathione depletion. By contrast, N-substituted N,O-dimethyl hydroxylamine (NODMH), primarily induces impairment of glucose 6-phosphate dehydrogenase (G6PDH) and glutathione reductase (GR). The oxidative potency of HYAM and the O-derivative was larger than the potency of the N,O-derivative. This seemed to indicate that attachment of an alkyl group to the nitrogen atom of hydroxylamine leads to decreased reactivity. To achieve a better understanding of the structure activity relationship for hydroxylamines three methylated derivatives were tested: N-methyl hydroxylamine (NMH). N-dimethyl hydroxylamine (NDMH) and O-methyl hydroxylamine (OMH). We were also interested in the erythrotoxic potency of OMH which recently entered industrial production. Methaemoglobin formation, high release of lipid peroxidation products, inhibition of NADPH methaemoglobin reductase and glutathione S-transferase (GST) and depletion of total glutathione (GT) were seen for OMH. The reducing enzymes G6PDH and GR were not impaired by OMH. These findings for OMH are consistent with the proposed mechanism for O-derivatives. Since both the effects caused by OMH and its potency are comparable to those of HYAM and OEH this indicates that possible occupational exposure to this compound may be approached similarly to HYAM and OEH. NMH only inhibited G6PDH and GR activity, which is fully in accord with the proposed mechanism for N-substituted derivatives of HYAM. However, NDMH a double N-substituted compound, caused a strikingly different scheme of reactivity inhibition of G6PDH but not of GR, severe methaemoglobin formation, only little lipid peroxidation and some impairment of NADPH methaemoglobin reductase. This study confirms that O-derivatives of HYAM are potent haemoglobin oxidators, leading to other oxidative effects. The main effect was confirmed for single N-derivatives as inhibition of the two protective enzymes G6PDH and GR. However, the results for NDMH indicate that this simple classification of O-derivatives and N-derivatives has to be extended for double N-substituted compounds which give a mixture of effects.
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PMID:In vitro haematotoxic effects of three methylated hydroxylamines. 913 8

The mechanism for ethanol-induced oxidative stress has been disputed because of the controversies on modulation of radical generating and scavenging activities by ethanol. In the present work, we attempted to clarify the acute effect of ethanol on the radical generating system as well as the radical scavenging system. For that purpose, chow-fed rats were given ethanol (5 g/kg) or isocaloric glucose solution by intragastric intubation and placed at 32 degrees C for 6 hr. Acute ethanol administration enhanced the expression of cytochrome P450 II E1(CYP II E1) in the liver and attenuated the activities of hepatic glutathione peroxidase (GPx) and reductase (GR). It also caused a significant increase in the level of hepatic thiobarbituric acid reactive substances (TBARS), an indicator of lipid peroxidation. On the other hand, acute ethanol feeding had no effect on the activities of catalase, xanthine oxidase (XO), glutathione transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH). From this result, it is suggested that acute ethanol administration causes the oxidative tissue damage by CYP II E1-associated radical generation and the decreased radical scavenging function due to the reduced activities of hepatic glutathione recycling system such as GPx and GR.
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PMID:Glutathione recycling is attenuated by acute ethanol feeding in rat liver. 928 31

The filamentous fungus Penicillium chrysogenum showed remarkable resistance to the oxidative stress caused by high concentrations of either hydrogen peroxide (0.35-0.70 M) or tert-butyl hydroperoxide (tert-BOOH, 0.5-2.0 mM), which could be explained well with high levels of glutathione (GSH) peroxidase and catalase activities. The majority of exogenous H2O2 was likely removed by catalase from the cells while tert-BOOH was likely eliminated mainly by the GSH-dependent pathways. The GSH pool decreased considerably at high tert-BOOH concentrations, the glutathione disulphide (GSSG) pool increased at high H2O2 and tert-BOOH concentrations, meanwhile all the peroxide concentrations tested increased markedly the intracellular peroxide concentration. All the enzyme activities taking part in the glutathione metabolism (glutathione peroxidase, glutathione reductase, gamma-glutamyltranspeptidase and glutathione producing activities) except glutathione S-transferase increased significantly after exposing mycelia to both peroxides while the specific glucose-6-phosphate dehydrogenase and catalase activities remained unchanged. In the presence of 0.5 mM diamide both GSSG and GSH concentrations as well as the glutathione reductase and glutathione producing activities were elevated but no significant changes were found in the intracellular peroxide concentration or in any of the other enzyme activities examined.
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PMID:Glutathione metabolism and protection against oxidative stress caused by peroxides in Penicillium chrysogenum. 929 59

There is no consensus yet on the role of oxidative stress in the nutritional outcome of chronic ethanol feeding and the status of cellular antioxidative defense systems against ethanol toxicity. In this study, chronic alcohol consumption in humans was reproduced in Sprague-Dawley rats to investigate the effect of ethanol ingestion on the regulation of oxidative stress in liver with a special focus on glutathione. Adult male rats were given 36% of total energy as alcohol in the Lieber-DeCarli liquid diet for 6 wk. The control group was pair-fed the diet containing isocaloric dextrin-maltose instead of ethanol. Chronic ethanol ingestion enhanced expression of cytochrome P450 II E1 in the liver, but did not significantly alter either the level of hepatic thiobarbituric acid reactive substances or the carbonyl group content of proteins. The hepatic concentrations of total and reduced glutathione and the activities of catalase, glutathione reductase and glutathione S-transferase were significantly higher in the ethanol group than in the control group. The activities of glutathione peroxidase and glucose-6-phosphate dehydrogenase were significantly lower in the ethanol group than in controls. Chronic ethanol consumption by well-nourished rats for 6 wk increased enzyme activities related to the recycling and utilization of glutathione in the liver. Such an enhancement in the activities of the hepatic antioxidative defense system may be one of the protective mechanisms of the body against oxidative tissue damage caused by ethanol-induced free radicals.
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PMID:Chronic ethanol consumption affects glutathione status in rat liver. 952 40

Vibrio cholerae O139 has pandemic potential and it produces copious amounts of fluid secretion. The levels of various second messengers (intracellular Ca2+, cAMP, IP3, PKC) were measured to determine the cause of fluid secretion produced by this strain of V. cholerae. There was a significant increase in the levels of these second messengers in V. cholerae O139 treated ileum as compared to control ileum (enterocytes). Levels of these second messengers were also assessed in V. cholerae 569B induced fluid secretion in rabbit ileum and it was found that the levels were raised more in V. cholerae O139 treated ileum than in V. cholerae 569B treated rabbit ileum. The intestinal damage was assessed by measuring changes in the extent of lipid peroxidation of the enterocytes. Intracellular second messengers are known to raise the extent of lipid peroxidation. In V. cholerae O139 treated loops calcium ionophore A23187 enhanced the extent of lipid peroxidation whereas l-verapamil could only marginally decrease the lipid peroxidation. Dantrolene and H7 significantly decreased the extent of lipid peroxidation of enterocytes in V. cholerae O139 treated rabbit ileum. However, PMA could not enhance further the extent of lipid peroxidation in V. cholerae O139 treated rabbit ileum. So intracellular calcium and protein kinase C appear to be involved in intestinal damage caused by V. cholerae O139. Reactive oxygen species are responsible for causing tissue damage and the extent of oxidative damage depends on the balance between the pro-oxidants and the anti-oxidants. So the changes in the enterocytes' antioxidant level during V. cholerae O139 mediated intestinal infection was estimated. There was a significant decrease in the enterocyte level of the antioxidant enzymes SOD, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase and glucose-6-phosphate dehydrogenase in V. cholerae O139 mediated intestinal infection. So a significant decrease in the levels of antioxidant defenses and a significant increase in the levels of second messengers appear to be important in mediating V. cholerae O139 induced lipid peroxidation which contributes to the changes in membrane permeability and thus to fluid secretion.
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PMID:Role of intracellular second messengers and reactive oxygen species in the pathophysiology of V. cholera O139 treated rabbit ileum. 963 66

Dopamine (DA) is oxidized to the neurotoxic prooxidant species H2O2, OH., and DA quinones. We tested whether dimethyl fumarate (DMF), an electrophile shown to induce a pleiotropic antioxidant response in nonneuronal cells, could reduce the toxicity of DA metabolites in neural cells. Treatment of the N18-RE-105 neuroblastoma-retina hybridoma cell line with 30-150 microM dopamine led to cell death within 24 h, which increased steeply with dose, decreased with higher plating density, and was blocked by the H2O2-metabolizing enzyme catalase. Pretreatment with DMF (30 microM, 24 h) significantly attenuated DA and H2O2 toxicity (40-60%) but not that caused by the calcium ionophore ionomycin. DMF treatment also elevated total intracellular GSH and increased activities of the antioxidant enzymes quinone reductase (QR), glutathione S-transferase (GST), glutathione reductase, and the pentose phosphate enzyme glucose-6-phosphate dehydrogenase. To assess the protective efficacy of QR and GST, a stable cell line was constructed in which these enzymes were overexpressed. Cell death in the overexpressing line was not significantly different from that in a cell line expressing normal QR and GST activities, indicating that these two enzymes alone are insufficient for protection against DA toxicity. Although the relative importance of a single antioxidant enzyme such as QR or GST may be small, antioxidant inducers such as DMF may prove valuable as agents that elicit a broad-spectrum neuroprotective response.
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PMID:Activation of endogenous antioxidant defenses in neuronal cells prevents free radical-mediated damage. 964 52

Ferric nitrilotriacetate (Fe-NTA) is a known complete renal carcinogen. In this study we show that Fe-NTA is a potent inducer of renal ornithine decarboxylase (ODC) activity and DNA synthesis and promoter of N-diethylnitrosamine (DEN)-induced renal tumorigenesis in rat. Fe-NTA induced renal ODC activity several fold as compared with saline-treated rats. Renal DNA synthesis, measured as [3H]thymidine incorporation into DNA, was increased after Fe-NTA treatment. Similar to other known tumor promoters, Fe-NTA also depleted the antioxidant armory of the tissue. It depleted glutathione (GSH) levels to approximately 55% of saline-treated controls. It also led to a dose-dependent decrease in the activities of glutathione reductase and glutathione S-transferase. Similarly, activities of catalase, glutathione peroxidase and glucose 6-phosphate dehydrogenase decreased significantly (45-65%). In contrast, gamma-glutamyl transpeptidase activity showed an increase. The maximum changes in activities of these enzymes could be observed at 12 h following Fe-NTA treatment. In addition, Fe-NTA augmented renal microsomal lipid peroxidation >150% over saline-treated controls, which was concomitant with the alterations in GSH metabolizing enzymes and depletion of the antioxidant armory. These effects were alleviated in rats which received a pretreatment with an antioxidant, BHA or BHT. Fe-NTA promoted DEN-induced renal tumorigenesis. In saline alone- and DEN alone-treated animals no tumors could be recorded, whereas in Fe-NTA alone-treated animals 17% tumor incidence was observed. However, in DEN-initiated and Fe-NTA-promoted animals tumor incidence increased to 71%. Our results show that Fe-NTA induces oxidative stress in the kidney and decreases antioxidant defenses, as indicated by the fall in GSH level and in the activities of glutathione peroxidase and catalase. Concomitantly, Fe-NTA increases ODC activity and DNA synthesis, which may be compensatory changes following oxidative injury to renal cells in addition to providing a strong stimulus for renal tumor promotion. Thus oxidative stress and impaired antioxidant defenses induced by Fe-NTA in the kidney may contribute to the observed nephrotoxicity and carcinogenicity.
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PMID:Ferric nitrilotriacetate promotes N-diethylnitrosamine-induced renal tumorigenesis in the rat: implications for the involvement of oxidative stress. 966 54

In order to understand the pulmonary toxicity of ultrafine titanium dioxide (UF-TiO2) particles, various biochemical and chemical parameters were assayed in rat alveolar macrophages (AMs) and cell-free lavage fluid. Single intratracheal exposure of UF-TiO2 (2 mg per rat) caused cytotoxicity to pulmonary AMs. An increase in the population of AMs could be observed, followed by increased activities of lactate dehydrogenase and acid phosphatase in cell-free lavage fluid. In addition, AMs showed an adaptive response because the activities of glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione S-transferase were increased in these cells. However, this enhancement of antioxidant enzymes could not diminish the enhanced lipid peroxidation and increased rate of hydrogen peroxide generation. The level of glutathione remained decreased in UF-TiO2-exposed rat AMs. The data suggest that the induction of antioxidant enzymes by these cells for self-protection is not sufficient to cope against the toxic action of UF-TiO2, which may lead to oxidative stress.
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PMID:Cytotoxicity, pro-oxidant effects and antioxidant depletion in rat lung alveolar macrophages exposed to ultrafine titanium dioxide. 980 29

The protective activity of small stress proteins (sHsp) against H2O2-mediated cell death in the highly sensitive murine L929 fibroblast has been analyzed. We report here that the human Hsp27- and murine Hsp25-mediated rise in glutathione (GSH) levels as well as the maintenance of this redox modulator in its reduced form was directly responsible for the protection observed at the level of cell morphology and mitochondrial membrane potential. sHsp expression also buffered the increase in protein oxidation following H2O2 treatment and protected several key enzymes against inactivation. In this case, however, the protection necessitated both an increase in GSH and the presence of sHsp per se since the pattern of protection against protein oxidation mediated by a simple GSH increase was different from that induced by sHsp expression. Among the enzymes analyzed, we noticed that sHsp significantly increased glucose-6-phosphate dehydrogenase (G6PD) activity and to a lesser extent glutathione reductase and glutathione transferase activities. Moreover, an increased GSH level was observed in G6PD-overexpressing L929 cell clones. Taken together our results suggest that sHsp protect against oxidative stress through a G6PD-dependent ability to increase and uphold GSH in its reduced form and by using this redox modulator as an essential parameter of their in vivo chaperone activity against oxidized proteins.
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PMID:Mammalian small stress proteins protect against oxidative stress through their ability to increase glucose-6-phosphate dehydrogenase activity and by maintaining optimal cellular detoxifying machinery. 1004 48


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