Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 cis-diamminedichloroplatinum (II) (CDDP)-resistant cell line (NOS2CR) demonstrated 7.4-fold greater resistance to CDDP compared with the parental cell line (NOS2) established from a patient with serous cystadenocarcinoma of the ovary. We investigated the role of enzyme systems associated with glutathione (GSH) in these cell lines. The GSH content was almost identical in both cell lines. Preincubation with 50 microM DL-buthionine-S, R-sulfoximine (BSO), an inhibitor of gamma-glutamyl cysteine synthetase, for 24 hr reduced the IC50 in both NOS2 and NOS2CR cells. Glutathione-S-transferase pi (GST-pi) activity and mRNA level in NOS2CR cells were higher than in NOS2 cells. However, gamma-glutamyltranspeptidase (GGT) activity in NOS2CR cells was 2.4-fold less than in NOS2 cells. The GST activity and mRNA level in both cell lines were constant when the cells were exposed to CDDP. Exposure to CDDP for 48 hr increased the GGT mRNA level 4.4 and 1.8 times in NOS2 and NOS2CR cells, respectively, compared with no exposure. By exposure to CDDP for 48 hr, the GGT activities in NOS2 and NOS2CR cells were increased 1.6-and 2.5-fold, respectively, compared with no exposure. The above data provide the first evidence that GGT activity and GGT mRNA are induced by CDDP in human carcinoma cell lines.
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PMID:Glutathione related enzymes in cis-diamminedichloroplatinum (II)-sensitive and-resistant human ovarian carcinoma cells. 790 18

2-Nitropropane (2-NP) or its anionic form propane 2-nitronate (P2-N) were tested as initiators in a sequential model of rat hepatocarcinogenesis, at the end of which preneoplastic foci were histologically detected. Six intraperitoneal (i.p.) injections of 25, 50 or 100 mg 2-NP or P2-N/kg body weight resulted in the appearance of liver gamma-glutamyltranspeptidase (gamma GT)- and glutathione S-transferase (GST-P)-positive foci, whose number and size increased with the dose of initiator. 2-NP and P2-N were equally effective. The potency of the highest dose (6 x 100 mg/kg body wt) was comparable to that of a single injection of diethylnitrosamine (100 or 200 mg/kg body wt). This work provides a short-term (70 days) and convenient model for further studies on 2-NP carcinogenicity.
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PMID:Induction of gamma GT- and GST-P positive foci in the liver of rats treated with 2-nitropropane or propane 2-nitronate. 791 May 13

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

The initiating potential of the secondary bile acids, deoxycholic acid (DCA) and lithocholic acid (LCA), was investigated using the development of preneoplastic lesions in the rat liver as a marker. In a short-term assay in which DCA and LCA were given in the diet for 3 weeks in conjunction with partial hepatectomy midway followed by the selection regimen, DCA dose-dependently induced gamma-glutamyltranspeptidase (gamma-GTP)-positive foci, but the results for LCA were less unequivocal and no dose-dependency was evident. In another experiment, I extended the period of observation and examined whether the gamma-GTP-positive foci thus induced by the secondary bile acids can develop into hepatic tumors after a latent period of 52 weeks with or without the administration of phenobarbital (PB), a promoter of experimental hepatocarcinogenesis. Whereas significantly high numbers of hyperplastic liver nodules developed in the DCA-treated rats irrespective of PB promotion, no such increase was evident in the LCA-treated rats. In contrast, both DCA and LCA treatments enhanced the development of glutathione S-transferase placental form (GST-P)-positive foci with or without subsequent PB promotion. The present data indicate that a short period of administration of DCA and LCA in the initiation stage in conjunction with partial hepatectomy results in enhanced development of preneoplastic liver lesions under selection pressure conditions with or without subsequent PB promotion. This suggests that these secondary bile acids possess possible initiating activity for rat hepatocarcinogenesis.
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PMID:[Studies on initiating activity of secondary bile acids for rat hepatocarcinogenesis]. 809 46

The effects of two aromatic thiocyanates, benzyl isothiocyanate (BITC) and benzyl thiocyanate (BTC), on diethylnitrosamine (DEN)-induced hepatocarcinogenesis were examined in rats. A total of 108 male ACI/N rats, 5 weeks old, were divided into 6 groups (18 rats in each). Group 1 was given a single i.p. injection of DEN (200 mg/kg body weight) one week after the start of the experiment and then kept on the basal diet until the end of the experiment (1 year). Groups 2 and 3 were treated with DEN and received dietary BITC (100 ppm) or BTC (100 ppm), respectively, throughout the experimental duration. Groups 4 and 5 were not given the carcinogen and were fed the diet containing BITC or BTC, respectively. Group 6 was kept on the basal diet alone and served as a control. Liver neoplasms were seen in Groups 1, 2 and 3. Incidence and average number of liver neoplasms in Group 2 were significantly smaller than in Group 1 (P < 0.0005 and P < 0.001, respectively). The incidence of liver neoplasms in Group 3 was slightly lower than in Group 1, although the difference was not statistically significant. The numbers of glutathione S-transferase placental form (GST-P)-positive foci in Group 2 and gamma-glutamyltranspeptidase (GGT)-positive foci in Groups 2 and 3 were significantly smaller than those in Group 1 (P < 0.001). The average and unit areas of GST-P- or GGT-positive foci in Group 2 or 3 were also significantly smaller than those in Group 1 (P < 0.05). These results suggest that BITC and BTC are chemopreventive agents for DEN-induced liver tumorigenesis.
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PMID:Inhibitory effects of benzyl isothiocyanate and benzyl thiocyanate on diethylnitrosamine-induced hepatocarcinogenesis in rats. 810 19

Plasma gamma-glutamyltranspeptidase (gamma-GT), glutathione peroxidase (GPx) and glutathione reductase (GR) activities were determined in normal and nasopharyngeal carcinoma (NPC) patients. No difference in enzyme activities was observed in the three major races of the Malaysian population, i.e. Malay, Chinese and Indian patients. However, plasma gamma-GT, erythrocyte glutathione S-transferase (GST) and GPx activities were significantly increased in all NPC patients, while GR activity remained unchanged. Patients with elevated plasma gamma-GT activities also had increased GST and GPx activities. Plasma gamma-GT and GPx activities were then found to be affected by treatment. Patients with plasma gamma-GT activity greater than 70 IU/l had very poor prognoses but patients with decreased gamma-GT activities were found to be in remission.
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PMID:Activities of gamma-glutamyl transpeptidase and erythrocyte glutathione dependent enzymes in nasopharyngeal carcinoma patients and normal controls. 810 26

It is known that phenobarbital (PB) and the peroxisome proliferator (PP) nafenopin (NAF) promote tumor formation by stimulating selective growth of different subtypes of liver foci. While PB enhanced the gamma-glutamyltranspeptidase (GGT)-positive eosinophilic-clear cell foci (ECF), NAF amplified the GGT-negative weakly basophilic foci (WBF). These findings provide the possibility of using the occurrence of these foci subtypes as early indicators for the carcinogenic potential of PB- and PP-type promoters. In order to improve the methods for the discrimination between ECF and WBF we studied further differences in their phenotype, as determined by the expression pattern of glutathione S-transferase (GST) subunits. GST subunits of the alpha (Ya, Yc), mu (Yb1, Yb2) and pi family (Yp), which compose different GST isoenzymes, were demonstrated by immunohistochemical methods. ECF were the only foci subpopulation that expressed GST subunit Yp, while this subunit was always absent in WBF and in another focus subtype, the tigroid foci (TF). Neither PB nor NAF changed this pattern. Thus Yp expression was rather a function of the focus type than of the promoter used. Upon PB treatment expression of the GST subunits Yb1 and Yb2 was frequently elevated in ECF, while Ya and Yc remained more or less unchanged. In NAF-treated livers large WBF, however, showed diminished expression of all investigated GST subunits of the alpha and mu family. In conclusion, PB seems to promote mostly ECF with elevated levels of mu and pi class GSTs, while low levels or absence of all GSTs tested may be associated with growth selection of WBF through the PP NAF.
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PMID:Glutathione S-transferase isoenzyme patterns in different subtypes of enzyme-altered rat liver foci treated with the peroxisome proliferator nafenopin or with phenobarbital. 824 72

Candida albicans is a dimorphic yeast capable of producing alternate morphological forms (yeast or mycelium) in response to environmental changes. The intracellular level of glutathione, which helps to maintain the redox potential of the cell, is decreased significantly during the thermal induction of yeast-to-mycelium conversion. The reason for the decline of glutathione in the mycelial form is not understood. We have, therefore, investigated the levels of glutathione reductase, glutathione S-transferase, gamma-glutamyltranspeptidase, and glutathione peroxidase, four key enzymes involved in glutathione metabolism, in the yeast and mycelial forms. Yeast cells of C. albicans 3153A were induced in Lee's medium (pH 6.5) at 37 degrees C for 3 h to produce germ tubes. Cell lysates were prepared from yeast and mycelial cells, and glutathione reductase, glutathione S-transferase, gamma-glutamyltranspeptidase, and glutathione peroxidase were assayed spectrophotometrically. There was a 640% increase of the level of gamma-glutamyltranspeptidase in the germ tubes as compared with the yeast cells. No other significant alteration of the levels of enzymes was noted. This increased activity of gamma-glutamyltranspeptidase, which cleaves the glutamic acid residue of glutathione (Glu-Cys-Gly) appears to be, at least in part, responsible for the rapid decrease of the intracellular glutathione in C. albicans during the yeast-to-mycelium conversion.
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PMID:Changes in glutathione metabolic enzymes during yeast-to-mycelium conversion of Candida albicans. 859

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

Candida albicans is a dimorphic pathogenic yeast capable of producing alternate morphological forms (yeast or mycelium) in response to environmental changes. The dimorphism of C. albicans plays an important role in the pathophysiology of this organism. The intracellular level of glutathione, which helps to maintain the oxidation-reduction potential of the cell, is decreased significantly during the yeast-to-mycelium conversion implicating the possible involvement of thiols in the yeast-to-mycelium transition. To evaluate the possible participation of sulphydryl group(s) containing component(s) in the yeast-to-mycelium transition of C. albicans, we examined the effect of a group of newly synthesized thiol-alkylators on the production of germ tubes from yeast cells. Several conjugated styryl ketones which are thiol-alkylators, and p-chloromercuriphenylsulphonate (a known nonpenetrating thiol-blocker) inhibited the yeast-to-mycelium conversion of C. albicans. The thiol-alkylators at 20 microM failed to inhibit four key enzymes (gamma-glutamyltranspeptidase, glutathione reductase, glutathione S-transferase and glutathione peroxidase) involved in glutathione utilization indicating that the inhibition of yeast-to-mycelium conversion is not mediated by the inhibition of glutathione metabolic enzymes. Moreover, these results suggest that a key thiol-blocker sensitive component(s) containing a critical sulphydryl group(s) is involved in the yeast-to-mycelium transition of C. albicans.
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PMID:Inhibition of yeast-to-mycelium conversion of Candida albicans by conjugated styryl ketones. 906 2


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