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

Reduced and oxidized glutathione and pyridine coenzymes, glutathione-related enzymes and Cu,Zn-superoxide dismutase (Cu,Zn-SOD) were investigated in the RBC of patients with chronic renal failure (CRF) and in age- and sex-matched controls. The effects of hemodialysis (HD) were also studied. A defective RBC redox state was shown in the CRF group based on a decreased GSH/GSSG ratio and NADPH levels. Increased activities of glutathione transferase (GSH-S-T) and Cu,Zn-SOD were observed before HD. Dialysis apparently restores the levels of antioxidant enzymes and at the same time strongly affects the redox state. Thus we can speculate that HD can generate severe redox impairment inducing damage in RBC and plasma antioxidant enzymes. Increased erythrocyte GSSG and GSM-S-T levels coupled with a reduced hexose monophosphate shunt (HMPS) function may be useful indexes of oxidative stress in uremic anemia.
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PMID:Erythrocyte redox state in uremic anemia: effects of hemodialysis and relevance of glutathione metabolism. 797 16

A human small cell lung cancer cell line, U-1906, developed altered functional properties upon continuous in vitro cultivation. Cells obtained at late (U-1906 L) and early (U-1906 E) passages of cultivation differ in drug resistance to the cytostatic therapeutic agents cisplatin and doxorubicin. The U-1906 L cells are 1.6-fold and 1.3-fold more resistant to cisplatin and doxorubicin respectively, than are the U-1906 E cells. In the more resistant U-1906 L cells, the total glutathione (GSH plus GSSG) level is 40% lower, whereas the activities of GSH-linked enzymes such as GSH peroxidase and GSH transferases are significantly higher. Quantitative analysis with isoenzyme-specific ELISAs demonstrated increased concentrations of all three of the measurable GSTs, M1-1, M3-3 and P1-1, in the more resistant cells. The intracellular protein expression patterns of the U-1906 E and the U-1906 L cells are very similar as revealed by two-dimensional denaturing electrophoresis, but show significant alterations in the concentrations of some components. Two 35 kDa proteins of different pI values, the concentrations of which are increased in the U-1906 L cells, were both identified as glyceraldehyde-3-phosphate dehydrogenase, either by N-terminal or by internal amino acid sequence analysis. The present study demonstrates that the increased resistance of the U-1906 L cells may involve multiple detoxification mechanisms and that the contribution of the GSH-linked detoxification can be ascribed to the elevation of cytosolic GST isoenzymes, GSH peroxidase and glutathione reductase, rather than to the intracellular GSH concentrations.
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PMID:Acquired resistance to cisplatin and doxorubicin in a small cell lung cancer cell line is correlated to elevated expression of glutathione-linked detoxification enzymes. 802 Jan 51

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

We studied the relation between the glutathione (GSH) system and cell proliferation in a model of smooth muscle cells (SMC) derived from the thoracic aorta of 4-6-week-old (young) and 15-month-old (aged) rats. SMC from aged rats showed greater levels of total non-protein thiol compounds (T-SH), increased glutathione transferase (GST) and increased glutathione reductase (GSSG-Red) activities compared with cells from young rats. These changes were associated with an increased proliferation rate of SMC from aged rats. To evaluate the role of GSH on cell proliferation better, a specific inhibitor of gamma-glutamyl-cystein synthetase, DL-buthionine-SR-sulphoximine (BSO) was used. BSO showed a dose-dependent inhibition of cell growth, with an IC50 of 10(-4) M, after 48-72 h of incubation. Removal of BSO restored cell growth, further suggesting a link between GSH levels and vascular cell proliferation. The inhibitory effect of BSO was about two times greater on SMC from young than on SMC from aged rats. BSO showed 56% inhibition on the proliferation of SMC from young rats and 32% inhibition on SMC from aged rats (10(-4) M, 72 h of incubation). A parallel reduction of GSH levels of 38% and 19% for SMC from young and aged rats, respectively, was observed, suggesting that age-related factors may influence the involvement of GSH system in cell proliferation.
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PMID:Differences in the glutathione system of cultured aortic smooth muscle cells from young and aged rats. 810 47

Established cell lines derived from newborn livers of c14CoS/c14CoS and cch/cch mice have been shown to be genetically resistant (14CoS/14CoS cells) or susceptible (ch/ch cells) to menadione toxicity. These differences are due in part to relatively higher levels of reduced glutathione (GSH) and NAD(P)H:menadione oxidoreductase (NMO1) activity in the 14CoS/14CoS cells. The indolic membrane-stabilizing antioxidant 5,10-dihydroindeno[1,2-b]indole (DHII) was shown previously to protect against various hepatotoxicants in vivo and in primary rat hepatocytes. This report describes how the 14CoS/14CoS and ch/ch cell lines provide a valuable experimental system to distinguish the mechanism of chemoprotection by DHII from menadione toxicity. The addition of 25 microM DHII produced a time-dependent decrease in menadione-mediated cell death in 14CoS/14CoS cells, with little effect on ch/ch cell viability. The maximum protective effect occurred at 24 hr, although the concentration of DHII remained constant for 48 hr. The protective effect of DHII correlated with enhanced glutathione levels (234% increase at 24hr), as well as induction of four enzymes involved in the detoxification and excretion of menadione: NAD(P)H:menadione oxidoreductase (NMO1, quinone reductase), glutathione reductase, glutathione transferase (GST1A1), and UDP glucuronosyltransferase (UGT1*06), with 24-hr maximum induction of 707, 201, 171 and 198%, respectively. Other biotransformation enzymes not directly involved in menadione metabolism (glutathione peroxidase, cytochromes P4501A1 and P4501A2, copper-, zinc-dependent superoxide dismutase, and NADPH cytochrome c oxidoreductase) were not induced by DHII. Menadione-stimulated superoxide production was inhibited 50% by DHII only in 14CoS/14CoS cells, and the inhibition required 24-hr preincubation. Pretreatment with DHII also protected both cell types against the menadione-mediated depletion of GSH, and the increase in percent (oxidized glutathione GSSG), an indicator of oxidative stress. These results suggest that DHII does not protect against menadione toxicity by virtue of its antioxidant or membrane-stabilizing properties. Rather, it acts by inducing a protective enzyme profile that migates redox cycling and facilitates excretion of menadione.
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PMID:Mechanisms of protection from menadione toxicity by 5,10-dihydroindeno[1,2,-b]indole in a sensitive and resistant mouse hepatocyte line. 824 Apr 1

The influence of acute diabetes (8 days), induced by streptozotocin (45 mg.kg-1 body weight) on myocardial and renal antioxidative conditions was investigated. The animals were given subtherapeutical doses of insulin (Interdep 6 U. kg-1 body weight, s.c.). Considerably increased levels of malondialdehyde (MDA), as well as of superoxide dismutase (SOD) and catalase (CAT) activity were found in the myocardium of diabetic animals. The oxidized glutathione (GSSG) level and glutathione peroxidase (GSH-PX) activity remained unchanged. The reduced glutathione (GSH) level as well as the activity of glutathione S-transferase (GST) were significantly lower. The activity of GSH-PX in the kidneys of diabetic rats increased by 60% and that of GST by 105%, respectively. CAT and SOD activity values were unchanged.
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PMID:Antioxidative state of the myocardium and kidneys in acute diabetic rats. 828 Jul 23

The erythrocytes from control (C), diabetic (D) and insulin-treated diabetic (D+I) rats were separated into three ageing groups (TAG) i.e., light dense (young cells), intermediate-dense (middle-aged cells) and heavy-dense (old aged cells) samples. The activities of enzymes and metabolites changed from young to old cells in the following manner: (1) Increase of CAT in TAG and a lower level in D and D+I (2) Decrease of GPx in TAG but a low level in D (3) Increase of GR in TAG but a higher level in D, (4) Increase of GST in C and a decrease in D with a higher level in young cells and a lower level in middle-aged and old cells. The reversal of enzyme was more in young cells of D+I (5) Increase of GSH in TAG, a low level in D and a high level in D+I (6) Increase of GSSG in TAG, a high level found only in young cells of D. The results show that young red cells are affected more significantly in diabetes than other age cell types.
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PMID:Ageing erythrocytes and alloxan diabetes: I. A possible role of catalase, GSH, GSSG, and GSH-enzymes in decreasing defence system. 829 96

Polychlorinated biphenyls are known to cause induction in cytochrome P450-dependent monooxygenase activities and alteration in the antioxidant defense of mammals. To determine whether similar detoxication processes are activated in rainbow trout (Oncorhynchus mykiss), we investigated P450-dependent enzyme activities, antioxidant enzymes and glutathione status (reduced and oxidized glutathione, GSH and GSSG) in this species injected intraperitoneally with 3,3',4,4'-tetrachlorobiphenyl at 5 mg/kg body weight 6 weeks post injection. Ethoxyresorufin O-deethylase activities increased 11- and 40-fold in liver and kidney. UDPglucuronosyltransferase activities were 2- and 5-fold higher in these organs, while glutathione S-transferase activity was enhanced greater than 2-fold in liver of tetrachlorobiphenyl injected trout in comparison with controls. Glutathione peroxidase activities were increased in liver and white muscle of dosed fish. Tetrachlorobiphenyl exposure resulted in a significant increase in glutathione reductase activities, with 7-fold enhancement in liver and significantly elevated activities in kidney, red and white muscles. Similarly, cytosolic superoxide dismutase and catalase activities were increased in white muscle of injected trout. Tetrachlorobiphenyl exposure significantly increased GSH concentrations in liver and kidney, while GSSG levels were increased in liver and blood plasma. These changes, however, did not modify the GSSG/GSH ratios in these tissues. Overall, these results imply a major tetrachlorobiphenyl effect on GSH status and antioxidant enzymes in trout tissues and identify white muscle along with liver and kidney as important tissues in the detoxication process in this animal.
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PMID:3,3',4,4'-tetrachlorobiphenyl effects on antioxidant enzymes and glutathione status in different tissues of rainbow trout. 857 41

Sulphur dioxide (SO2) is an air pollutant implicated in the initiation of asthmatic symptoms. Glutathione (GSH) has been proposed to play a role in detoxification of SO2 through the sulfitolysis of glutathione disulphide (GSSG) to S-sulphoglutathione (GSSO3-). Rats were exposed to concentrations of SO2 between 5 and 100 ppm for 5 hr a day between 7 and 28 days. Lung injury as assessed by bronchoalveolar lavage and tissue GSH status were evaluated. SO2 5 ppm failed to elicit any lung injury or inflammatory response but did deplete GSH pools in lung, liver, heart and kidney. Activities of gamma-glutamylcysteine synthetase (GCS), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GRed) in lung were lowered relative to those in control animals. In liver, GRed activity was decreased. SO2 50 ppm exposure also failed to elicit injury or inflammation but did lower inflammatory cell numbers in the circulation. Rats exposed to 50 ppm SO2 maintained tissue GSH status, but activities of GCS, GPx, GRed and gamma-glutamyltranspeptidase in lung and hepatic GRed and GPx were significantly lower than in control rats. Unaltered GST activity in lung and liver was suggestive of an impairment of the sulfitolysis reaction in these animals, perhaps through lower substrate flux through the GPx reaction, as GSSO3- is a known inhibitor of GST in the rat. Rats exposed to 100 ppm SO2 exhibited evidence of inflammation (120-fold increase in neutrophil numbers recovered in lavage fluid) and like the 5 ppm exposed rats had lower tissue GSH concentrations and GSH-related enzyme activities in lung. We conclude that sulfitolysis of GSSG does occur in vivo during SO2 exposure and that SO2, even in the absence of pulmonary injury, is a potent glutathione depleting agent.
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PMID:Sulphur dioxide: a potent glutathione depleting agent. 876 Jun 4


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