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)

1. Six enzymes which collectively catalyze a number of glutathione-dependent synthetic, catabolic and detoxification reactions were examined along with glutathione status in liver, gills, and posterior kidney of channel catfish (Ictalurus punctatus). 2. Hepatic GSH concentrations were higher than those in kidney or gills. Oxidized glutathione (GSSG) concentrations were similar among the three tissues. 3. Specific (per unit protein) gamma-glutamylcysteine synthetase (GCS) activity was greater in the gills than in liver or posterior kidney. However, total organ GCS activity was greatest in the liver. 4. Specific and total hepatic glutathione peroxidase (GSH peroxidase) activities were substantially greater than those of gills or kidney. 5. Similar specific glutathione reductase (GSSG reductase) activities were observed among all three tissues. 6. All three tissues exhibited glutathione S-transferase (GST) activity towards 1-chloro-2,4-dinitrobenzene (CDNB). Specific and total organ GST activities were highest in the liver, followed by the posterior kidney and gills. 7. Gamma-glutamyltranspeptidase (GGT) activity was present in the posterior kidney, but was undetectable in the gills or liver.
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PMID:A comparison of glutathione-dependent enzymes in liver, gills and posterior kidney of channel catfish (Ictalurus punctatus). 136 Mar 60

The effect of bucillamine (BA) on glutathione (GSH) and GSH-related enzymes was investigated in C57 mouse. Administration of high doses of BA (150-400 mg/kg) produced a dose-dependent depletion (20-44%) of hepatic GSH, which was similar in magnitude to that produced by equimolar doses of other sulphydryl drugs studied previously. GSH depletion after acute BA administration correlated well with the elevation of serum glutamic-pyruvic transaminase (SGPT) (6-9-fold increase above control). The increase in SGPT after chronic administration (7 days), although significantly higher than the controls, was however much less than after acute administration. The hepatic GSH concentrations of mice given 7 days of BA were similar to the controls, again correlating well with SGPT activity. Administration of BA (150-400 mg/kg) caused also a significant dose-dependent increase in the oxidized glutathione (GSSG) in blood by 2-7-fold, as well as a dose-dependent increase in blood glutathione S-transferase (GST) activity (2-13-fold). In an in vitro experiment, hepatic GST activity was activated by various concentrations of BA (1 microM-1mM). There was little or no effect on GSSG reductase and on glutathione peroxidase (GSH-Px) after acute administration of BA. Chronic administration of BA had no effect on hepatic GSSG reductase and GSH-Px, but GSSG reductase activity in blood was increased significantly by 4-fold. It is possible that BA may affect the redox status through auto-oxidation and oxidation with endogenous thiols such as glutathione, affecting GSH concentrations and the GSH/GSSG ratio in tissues and, thus, having both metabolic and toxicological consequences. Whether or not the induction of GST activity in vivo in blood and in vitro in liver enzyme preparations shared the same underlying mechanism(s) requires further investigation.
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PMID:The effects of bucillamine on glutathione and glutathione-related enzymes in the mouse. 186 40

The activities of tissue glutathione (reduced and oxidized) and glutathione-dependent enzymes such as glutathione S-transferase (GSH S-transferase), glutathione reductase (GSSG reductase) and glutathione peroxidase (GSH-Px) were determined for control and uremic rats. Acute renal failure (ARF) was produced by glycerol-water injection. Cytosolic and microsomal GSH S-transferase activity in the kidney was decreased by 38% and 15%, respectively. Hepatic microsomal GSH S-transferase was also decreased by 40% in uremic rats. GSH-Px activity was decreased by 51% in the cytosolic fraction and 33% in the microsomal fraction in the kidney, but was not affected in the liver and whole blood. GSSG reductase activity was also decreased by 48% in the cytosolic fraction in the kidney of uremic rats. In whole blood, however, GSSG reductase activity was increased by 12-fold (0.66 +/- 0.12 mumol NADPH oxidized/min/ml blood in the control; 8.03 +/- 3.29 mumol NADPH oxidized/min/ml blood in uremia). Although the total glutathione concentrations were not significantly affected, the GSSG/GSH ratio, which is an indication of oxidative stress, was significantly increased in the liver and whole blood of uremic rats. In addition to the decreases in hepatic and renal GSH S-transferase activities, which is important in drug disposition, ARF caused decreases in GSSG reductase and GSH-Px activity, which are essential for the protection against lipid peroxidation.
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PMID:Effects of glycerol-induced acute renal failure on tissue glutathione and glutathione-dependent enzymes in the rat. 187 Mar 54

In the present study we have compared the levels of glutathione (GSH) S-transferase, GSH peroxidase and GSH reductase in human breast tumors and adjacent normal tissues obtained from the same individuals. We have also quantitated GST pi type antigen in these samples by western blotting. GST pi activity towards 1-chloro-2,4-dinitrobenzene was found to be elevated in tumors from three out of six patients (patient nos. 2, 4 and 5), whereas this activity was suppressed in tumor from patient no. 1. Results of Western blotting using antibodies raised against GST pi of human placenta were in agreement with the GST activity data. GSH peroxidase activity with cumene hydroperoxide as substrate was found to be elevated in four tumor samples (patient nos. 2, 4, 5, and 6) but suppressed in tumor from patient no. 1. On the other hand, GSH reductase activity was elevated in three samples (patients nos. 2, 4 and 5) and downregulated in the remaining three samples (patients nos. 1, 3 and 6). These results indicate that GSH-related enzymes are differentially altered in human breast tumors and GST pi type isoenzyme(s), unlike certain other human carcinomas such as colonic, are not uniformly elevated in human breast tumors.
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PMID:Differential expression of glutathione S-transferase, glutathione peroxidase and glutathione reductase in normal and malignant human breast tissues. 233 97

Friend erythroleukemia cells (FLC) selected by exposure to Adriamycin (doxorubicin) express an approximate 2.5-fold (ARN1) or 13-fold (ARN2) resistance to the drug with various degrees of cross-resistance to other anthracyclines, vinca alkaloids, and epipodophyllotoxins. Because the redox cycling of the quinone moiety of Adriamycin is known to produce oxidative stress, however, an analysis of glutathione (GSH) and related enzyme systems was undertaken in the wild-type and selected resistant cells. In ARN1 and ARN2, superoxide dismutase (SOD) and catalase activities were slightly decreased, intracellular GSH and GSH reductase were essentially unchanged, and total GSH peroxidase, glutathione S-transferase (GST), and DT-diaphorase activities were slightly elevated. In each case there was no stoichiometric relationship between degree of resistance and level of activity. GST isozymes were purified from each cell line by HPLC GSH affinity column chromatography. Two-dimensional gel electrophoresis and western blot immunoreactivity against a battery of GST isozyme polyclonal antibodies determined that both the resistant and sensitive cells expressed isozymes of the alpha, pi, and mu classes (alternative murine nomenclature: M1, M2, M3). Of significance, both ARN1 and ARN2 cell lines expressed a unique alpha subunit which was absent from the parent FLC cell line. This isozyme presumably accounted for the increased GSH peroxidase activity (cumene hydroperoxide as substrate) found in ARN1 and ARN2 and may play a role in the small incremental resistance to melphalan found for both resistant lines. Expression of the isozyme was not stoichiometric with respect to degree of resistance. The presence of this isozyme may contribute to the resistant phenotype or may be the consequence of a more general cellular response to oxidative stress.
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PMID:Glutathione, glutathione S-transferases, and related redox enzymes in Adriamycin-resistant cell lines with a multidrug resistant phenotype. 263 24

The use of monochlorobimane (MCIB) as a fluorescence label for glutathione (GSH) quantitation was investigated in human tumor cell lines. When MCIB was used with a hamster fibroblast cell line under conditions where GSH was either depleted or elevated, an excellent correlation between bimane-GSH fluorescence and the standard cyclic GSH reductase assay (Tietze's) was accomplished. When the MCIB technique was applied to a human lung adenocarcinoma cell line, little or no GSH labeling was noted even at MCIB levels 10X higher than that used for the hamster line. HPLC analysis suggested that the source of the problem may be the affinity for MCIB to glutathione S-transferase. By using higher dye concentrations and longer staining times, adequate staining was possible. While the MCIB technique may have problems quantitating GSH levels between cell types, the possibility of examining GSH heterogeneity in solid tumor biopsies remains feasible.
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PMID:Use of monochlorobimane for glutathione measurements in hamster and human tumor cell lines. 271 86

In the present studies we have compared the levels of glutathione (GSH) and GSH-related enzymes in lung tumors and corresponding normal tissues obtained from the same individuals. We have also immunologically quantitated the relative amounts of glutathione S-transferase pi (or GST-P) type antigen in tumors and adjacent normal tissues from five patients. GST activities towards 1-chloro-2,4-dinitrobenzene (CDNB) and ethacrynic acid were found to be elevated in tumors from two out of five patients (patients #1 and 4), whereas the activity towards these substrates was markedly suppressed in the tumor tissue from one of the patients (#5). Immunotitration and Western blot studies using antibodies raised against pi-type GST isoenzymes of human lung and placenta indicated induction of GST pi-type isoenzyme in tumors from patients #1 and 4 and suppression of this isoenzyme in tumor from patient #5. The tumors from patients #2 and 3 did not show any increase in GST activity or GST pi-type antigen. Except for the tumor from patient #5, the GSH content was higher in the tumors from other patients. GSH reductase activity was found to be elevated in tumors of all the patients examined in this study. These results indicate that GSH and GSH related enzymes are differentially altered in lung tumors and GSH levels and GST pi- or GST-P-type isoenzyme(s) are not uniformly elevated in all tumors.
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PMID:Glutathione S-transferase isoenzymes in human lung tumors. 340 73

Periportal and perivenous hepatocytes were isolated by the digitonin-collagenase perfusion technique. The activity of the cytosolic glutathione S-transferase was higher in perivenous cells, but the cytosolic glutathione reductase and the microsomal glutathione S-transferase activities were evenly distributed. In contrast, both the Se-dependent and the microsomal Se-independent glutathione peroxidase activity and the glucose-6-phosphate dehydrogenase activity was much lower in perivenous hepatocytes, suggesting that these cells have a lowered detoxification capacity, which may contribute to their greater susceptibility to damage by xenobiotics. The mechanism of the ethanol-induced GSH depletion in vivo was studied by incubating conventionally isolated hepatocytes. In the absence of glutathione precursors, ethanol (80 mM) did not influence the GSH content, despite accumulation of acetaldehyde (10-100 MicroM). L-Methionine or L-cysteine stimulated GSH replenishment to in vivo rates. Ethanol oxidation resulted in acetaldehyde accumulation, but did not inhibit GSH replenishment from L-methionine and even stimulated that from L-cysteine. This seems to exclude conjugation of GSH with acetaldehyde as a mechanism by which ethanol suppresses GSH levels in vivo.
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PMID:Glutathione metabolism in isolated rat hepatocytes: acinar heterogeneity of detoxifying enzymes and effects of ethanol. 342 86

We review the role of glutathione (GSH) and its metabolizing enzymes, glutathione S-transferase (GST) and glutathione reductase (GSR) in drug metabolism and in the elimination of foreign compounds. Levels of GSH and the activity of these enzymes may be greatly influenced by drugs and other substances in the body. We therefore determined GSH levels and the activities of GST and GSR in human erythrocytes and lymphocytes in males and females in three age groups. There was no significant difference between males and females in the three age groups in respect of GSH levels and GST and GSR activities. GSH levels in erythrocytes were higher than those in lymphocytes when expressed per mg protein, but lower than those in lymphocytes when expressed per 10(6) cells. The activities of both GST and GSR were found to be higher in lymphocytes than in erythrocytes.
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PMID:Glutathione, glutathione S-transferase and glutathione reductase in human erythrocytes and lymphocytes as a function of sex. 350 37

Toxic effects of SO2 and sulfite such as bronchitis and bronchoconstriction have been well documented. SO2 has also been suggested to potentiate carcinogenic effects of PAH. However, the molecular basis of these toxic effects is unclear. We have examined the covalent reaction of SO2 and sulfite with cellular proteinacious and nonproteinaceous sulfhydryl compounds using rat liver, and lung and human lung derived A549 cells. Reactions of sulfite and protein in rat and human lung cells reveals at least three proteins with sulfite-reactive disulfide bonds. Besides fibronectin and serum albumin, which had been reported to contain sulfonated products following exposure to sulfite, we have found one other protein with sulfite-binding capabilities. Since the integrity of disulfide bonds is crucial to the tertiary structure and thus protein function, the disruption of protein structure by sulfitolysis may result in altered cellular activities leading to biochemical lesions. Using carefully controlled conditions, reproducible GSH contents can be found in cultured cells and used as an experimental basis for studying alterations in the GSH and GSSG content of cells. Sulfitolysis of GSSG results in the formation of GSSO3H in A549 cells, and possibly in the lung. GSSO3H can be reduced enzymatically by GSSG reductase. However, the Km of GSSO3H is high compared to that of GSSG, suggesting the existence of a transient concentration of GSSO3H once it is formed. Cysteine S-sulfonate is, however, not reduced by cytosolic extracts in the presence of NADPH and would have to be eliminated from the cell by other means. GSSO3H is a strong competitive inhibitor of GST in rat liver and lung and A549 cells, using 1-chloro-2,4-dinitrobenzene as a substrate. It also inhibits the formation of GSH conjugates of BP 4,5-oxide, anti and syn BPDE, but to a lesser extent. These results suggest that SO2 may affect the detoxification of xenobiotic compounds by inhibiting, via formation of GSSO3H, the enzymatic conjugation of GSH and reactive electrophiles. Since GSH conjugation represents the major pathway of elimination of BP epoxides in the lung, our results offer a possible explanation for the cocarcinogenicity of SO2 with PAHs. These data suggest that the sulfitolysis reaction of sulfite is the common reaction mechanism mediating the underlying biochemical reactions leading to both the toxic and cocarcinogenic properties of SO2. Quantitation of sulfitolysis products and their interaction with cellular processes should provide a coherent scheme relating SO2 and sulfite toxicity among animal species and humans.
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PMID:Covalent reactions in the toxicity of SO2 and sulfite. 376 76


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