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)

Studies were performed to determine the effects of chronic hypoxia on enzymes that catalyze various detoxication reactions. Rats were exposed to room air or 10.5% O2 for 10 days, and microsomes and postmicrosomal supernatants were isolated from liver. Detoxication enzyme activities were measured by radiochemical and spectrophotometric assays, and immunoreactive protein amounts were measured by Western blot analysis. Total cytochrome P450, as measured by the CO-difference spectrum, and activities of superoxide dismutase (EC 1.15.1.1), epoxide hydrolase (EC 4.2.1.63), catalase (EC 1.11.1.6), glutathione disulfide reductase (EC 1.6.4.2), and glutathione (GSH) S-transferase (EC 2.5.1.18) were not affected by this extent of hypoxia. In contrast, 10 days of hypoxia decreased activities or immunoreactivities (% of aerobic) of GSH peroxidase (EC 1.11.1.9) (54%), cytochrome P450EtOH2 (42%), CYP3A1 (53%), sulfotransferase (EC 2.8.2.1) (77%) and UDP-glucuronosyltransferase (EC 2.4.1.17) (65%). Activity of glucose-6-phosphate dehydrogenase (EC 1.1.1.49), an important enzyme in NADPH production was also decreased to 56% of the aerobic value, but Western blot analysis showed that the amount of protein reactive with antibodies to glucose-6-phosphate dehydrogenase was not affected by hypoxia. Thus, hypoxia may decrease activity of enzymes by regulatory mechanisms even though the amount of immuno-detectable enzyme is unchanged. Liver cells isolated from rats exposed to hypoxia also gave lower GSH synthetic rates than cells from normoxic rats. This result, together with the effect of hypoxia on glucose-6-phosphate dehydrogenase, indicates that the GSH supply for GSH-dependent detoxication reactions may be limited due to chronic hypoxia. To test directly whether chronic hypoxia increased sensitivity to a compound normally detoxified by a GSH-dependent reaction, sensitivity to tert-butyl hydroperoxide (t-BuOOH) of hepatocytes from rats exposed to in vivo hypoxia was compared to that from normoxic rats. The results showed that the cells from the hypoxic rats were much more sensitive to injury. Taken together, these results suggest that decreases in amounts and/or activities of detoxication enzymes during chronic hypoxia may result in increased susceptibility of cells to chemical injury.
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PMID:Effect of chronic hypoxia on detoxication enzymes in rat liver. 161 Apr 6

The present work tries to establish the antioxidant capacity of the peripheral nervous tissue of the rat, in terms of the enzymatic activities present in this tissue that either prevent the formation of activated species as the semiquinone radical (DT-diaphorase), protect against activated oxygen species (superoxide dismutase, glutathione peroxidase), conjugate natural toxic products or xenobiotics (glutathione S-transferase, especially the activity conjugating 4-hydroxy-nonenal), or complete the glutathione system metabolism (glutathione disulfide reductase, gamma-glutamyl transpeptidase). All the activities studied are lower in this tissue than they are in liver, except for gamma-glutamyl transpeptidase. The relevance of the results obtained and its possible relationship with different neuropathies is discussed. It is concluded that the peripheral nervous tissue is by far less protected than the liver against oxidative damage.
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PMID:Antioxidant and glutathione-related enzymatic activities in rat sciatic nerve. 197 22

Strain differences of mice in their susceptibility to nitrogen dioxide (NO2) were examined by measuring the activities of antioxidative protective enzymes, and the amounts of antioxidants and lipid peroxides in lungs. Four strains of mice: ICR, BALB/c, ddy and C57BL/6 were used in this study and their LC50 values after exposure to NO2 for 16 hr were: 38, 49, 51 and 64 ppm, respectively (1). Genetic strain differences were observed in the enzyme activities, the antioxidant contents and lipid peroxide contents among these four different strains. The activities of glutathione peroxidase (GPX), glutathione S-transferase, and superoxide dismutase (SOD), and the contents of non-protein sulfhydryls (NPSH), alpha-tocopherol (alpha-Toc) and total lipids in lungs of the four strains were related to their LC50, while TBA reactants in lungs of the four strains were inversely related to their LC50. After exposure to 20 ppm NO2 for 16 hr, the activities of the protective enzymes and the contents of NPSH decreased, while the level of alpha-Toc increased markedly. The activities of GPX, 6-phosphogluconate dehydrogenase, SOD and disulfide reductase, and the contents of NPSH, alpha-Toc and total lipids were also related to their LC50. On the other hand, TBA reactants increased higher than those of the control groups and were inversely related to their LC50. These results suggest that the protective enzymes and the antioxidants are important factors at defence mechanism in lungs to NO2 and that the intensity of the protective systems in pigmented strains is generally greater than that in albino strains.
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PMID:Biochemical studies on strain differences of mice in the susceptibility to nitrogen dioxide. 717 5

The recovery of glutathione and its metabolising enzymes (glutathione disulfide reductase, glutathione peroxidase, thiol transferase, gamma-glutamyl transpeptidase and glutathione transferase) along with sulfhydryl groups and byproduct of lipid peroxidation (malondialdehyde) in the brain, spinal cord, kidney and liver of mice, altered during methylmercury chloride (MMC) intoxication, is recorded in post-therapeutic treatment with vitamins and monothiols. For this purpose ten groups of animals were intoxicated with 1 mg/kg MMC/day for 7 days. Out of these, one group was sacrificed on 8th day and one group was kept without toxicant for another seven days before sacrificing on 15th day. Study shows significant decrease of various biomolecules of glutathione metabolism during MMC application, which are further decreased with increasing the duration on 15th day. The trend is same in all the tissues with few exceptions. However, malondialdehyde, a byproduct of lipid peroxidation, is increased with increasing the duration after intoxication. Study also shows a significant recovery (in many cases a complete control level) of most of the components with one or the other chelator or with their combined therapy. Therefore, it is concluded from overall study that vitamins B complex and E, GSH (or its precursor NAHT) either alone or in combinations, are quite suitable for methylmercury post-therapy.
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PMID:Ameliorative capacities of vitamins and monothiols post therapy in the restoration of methylmercury altered glutathione metabolism. 791 95

The major aspects of the glutathione (GSH)-related antioxidant defense of human retina are presented. These include concentration of GSH and activities of some GSH-dependent enzymes: glutathione peroxidase, glutathione disulfide reductase, and glutathione S-transferase toward a broad spectrum substrate 1-chlor-2,4-dinitrobenzene and a toxic product of lipid peroxidation (4-hydroxynonenal). The presence of a relatively high GSH concentration, GSH peroxidase activity, and GSH S-transferase specific activity toward 4-hydroxynonenal in human retina might constitute a central defense mechanism in inflammation-promoted oxidative stress and subsequent lipid peroxidation. The use of different substrates for the determination of the GSH peroxidase activity showed no statistically significant difference, thus suggesting the lack of Se-independent GSH peroxidase in human retina. Large individual variations were obtained for GSH concentration and the different activities tested; the apparent correlation with age of these findings is currently under investigation.
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PMID:Glutathione system of human retina: enzymatic conjugation of lipid peroxidation products. 834 44

The expression of glutathione (GSH)-dependent enzymes and cytochrome P450 (P450) proteins in freshly isolated proximal tubular cells from human kidney (hPT), and the effect of primary culture on these enzymes, were determined. Freshly isolated hPT cells had relatively high activities of gamma-glutamyltransferase, gamma-glutamylcysteine synthetase, glutathione S-transferase (GST), glutathione disulfide reductase, and GSH peroxidase. Cytochrome P450 4A11 was detected in freshly isolated hPT cells, whereas CYP2E1 was not. Freshly isolated hPT cells also expressed GSTA, GSTP, and GSTT but not GSTM. Primary cultures of hPT cells maintained their epithelial-like nature and diploid status, based on measurements of morphology, cytokeratin expression, and flow cytometric analysis. hPT cells retained GSH-dependent enzyme activities during primary culture, whereas cells that had undergone subsequent passage exhibited a loss of activities of most GSH-dependent enzymes and no longer expressed P450s or GSTs. CYP4A11 expression in primary cultures of hPT cells was significantly increased after treatment for 48 h with either ethanol (50 mM) or dexamethasone (7 nM). GSTA, GSTP, and GSTT contents, although still detectable, were decreased compared with those of freshly isolated hPT cells. Our data show that hPT cells express enzymes involved in xenobiotic disposition, and that they thus provide a model suitable for studies of human renal drug metabolism. Furthermore, primary cultures of hPT cells may afford the opportunity to study factors regulating P450 enzyme expression in human kidney.
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PMID:Expression of glutathione-dependent enzymes and cytochrome P450s in freshly isolated and primary cultures of proximal tubular cells from human kidney. 1077 44

The aims of our study were to assess whether endurance training strengthens glutathione-dependent antioxidant defenses and decreases oxidative stress in experimental diabetes. Streptozotocin-induced diabetic rats were divided into trained and untrained groups, which were further divided into resting and acute exercise groups. Endurance training consisted of treadmill running for 8 weeks. For acute exhaustive exercise, graded treadmill running was conducted until exhaustion. Eight weeks' treadmill training increased the endurance, favorably decreased lipid peroxidation as measured by thiobarbituric acid reactive substances but not conjugated dienes levels in kidney and vastus lateralis muscle and upregulated glutathione peroxidase in red gastrocnemius muscle. However, it adversely decreased total glutathione level and glutathione peroxidase activity in kidney. Acute exhaustive exercise up-regulated glutathione peroxidase activity in liver. Endurance training did not prevent the increase in thiobarbituric acid reactive substances level in liver due to acute exhaustive exercise. Activities of glutathione disulfide reductase and glutathione S-transferase were not affected. Even though endurance training appeared to upregulate glutathione dependent antioxidant defense in skeletal muscle and to decrease lipid peroxidation in kidney and vastus lateralis muscle as measured by TBARS, our results suggests that beneficial effects of 8 weeks of endurance training are limited in this rat model of uncontrolled diabetes mellitus.
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PMID:Effects of endurance training on tissue glutathione homeostasis and lipid peroxidation in streptozotocin-induced diabetic rats. 1213 49

Thioredoxin is ubiquitous and regulates various target proteins through disulfide bond reduction. We report the structure of thioredoxin (HvTrxh2 from barley) in a reaction intermediate complex with a protein substrate, barley alpha-amylase/subtilisin inhibitor (BASI). The crystal structure of this mixed disulfide shows a conserved hydrophobic motif in thioredoxin interacting with a sequence of residues from BASI through van der Waals contacts and backbone-backbone hydrogen bonds. The observed structural complementarity suggests that the recognition of features around protein disulfides plays a major role in the specificity and protein disulfide reductase activity of thioredoxin. This novel insight into the function of thioredoxin constitutes a basis for comprehensive understanding of its biological role. Moreover, comparison with structurally related proteins shows that thioredoxin shares a mechanism with glutaredoxin and glutathione transferase for correctly positioning substrate cysteine residues at the catalytic groups but possesses a unique structural element that allows recognition of protein disulfides.
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PMID:Structural basis for target protein recognition by the protein disulfide reductase thioredoxin. 1709 95

Glutaredoxins (Grxs) are a ubiquitous family of proteins that reduce disulfide bonds in substrate proteins using electrons from reduced glutathione (GSH). The yeast Saccharomyces cerevisiae Grx6 is a monothiol Grx that is localized in the endoplasmic reticulum and Golgi compartments. Grx6 consists of three segments, a putative signal peptide (M1-I36), an N-terminal domain (K37-T110), and a C-terminal Grx domain (K111-N231, designated Grx6C). Compared to the classic dithiol glutaredoxin Grx1, Grx6 has a lower glutathione disulfide reductase activity but a higher glutathione S-transferase activity. In addition, similar to human Grx2, Grx6 binds GSH via an iron-sulfur cluster in vitro. The N-terminal domain is essential for noncovalent dimerization, but not required for either of the above activities. The crystal structure of Grx6C at 1.5 A resolution revealed a novel two-strand antiparallel beta-sheet opposite the GSH binding groove. This extra beta-sheet might also exist in yeast Grx7 and in a group of putative Grxs in lower organisms, suggesting that Grx6 might represent the first member of a novel Grx subfamily.
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PMID:Structural and biochemical characterization of yeast monothiol glutaredoxin Grx6. 2034 49