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

---

Query: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies on glutathione metabolism in an established baby hamster kidney cell line (BHK-21/C13) and in its polyoma virus-transformed counterpart (BHK-21/PyY), have revealed a significant stimulation of intracellular glutathione peroxidase activity (Se-independent plus Se-dependent) by alpha-tocopherol supplementation (14 microM). This stimulation was found to be much greater in the transformed cells. Other GSH-requiring enzyme activities (namely glutathione reductase and glutathione transferase) were unaltered by alpha-tocopherol treatment, suggesting a degree of specificity in its action on GSHpx. In unsupplemented growth media, the GSHpx activity in both cell lines was significantly decreased by an oxidative stress. However, the same stress applied to the alpha-tocopherol-supplemented cells had no effect on the stimulated GSHpx activity, suggesting a protection afforded by the alpha-tocopherol.
...
PMID:Variable alpha-tocopherol stimulation and protection of glutathione peroxidase activity in non-transformed and transformed fibroblasts. 133 9

These studies concern the initial steps in 4-nitroquinoline 1-oxide (4NQO) metabolism in relation to mechanisms of anticarcinogenesis. Butylated hydroxyanisole (BHA) administration by a protocol known to inhibit the pulmonary tumorigenicity of 4NQO in A/HeJ mice enhanced hepatic and pulmonary activities for 4NQO metabolism by two major pathways, conjugative detoxification and nitroreductive activation. High-performance liquid chromatography analysis showed approximate doubling of two types of glutathione transferase subunits with 4NQO-conjugating activity in livers of BHA-treated mice. Similar increases were observed in hepatic 4NQO-conjugating activity and in Vmax, while Km for 4NQO was 39 to 43 microM. Pulmonary 4NQO-glutathione transferase activity increased 24 to 29%. DT diaphorase activity toward 4NQO was elevated 3.3-fold in livers and 2.7-fold in lungs of BHA-treated mice. However, the predominant 4NQO reductase of liver and lung was dicumarol resistant, had a strong preference for NADH, and showed little if any response to BHA. This Mr 200,000 enzyme, partially purified from livers of Swiss mice, exhibited the stoichiometry of 2-NADH/4NQO expected for reduction of 4NQO to 4-hydroxyaminoquinoline 1-oxide. Its high affinity for 4NQO (Km, 15 microM) signified a much greater influence on 4NQO metabolism than DT diaphorase (Km, 208 microM). The dicumarol-resistant 4NQO reductase differed from several known cytosolic nitroreductases. The results suggest that protection by BHA may result from alteration of the balance between 4NQO activation and conjugation.
...
PMID:Nitroreductases and glutathione transferases that act on 4-nitroquinoline 1-oxide and their differential induction by butylated hydroxyanisole in mice. 137 76

Stromal cells from bone marrow are susceptible to toxicity induced by several redox-active metabolites of benzene, including hydroquinone (HQ). We have previously shown that tert-butyl-hydroquinone (tBHQ) can induce quinone reductase (QR) in bone marrow stroma as well as protect stromal cells against HQ-induced toxicity. Current studies investigate the underlining mechanisms of chemoprotection against HQ in DBA/2- and C57Bl/6-derived bone marrow stromal cells. The chemoprotector 1,2-dithiole-3-thione (DTT) has been used in these studies due to tBHQ toxicity to stromal cells at higher concentrations. Pretreatment of cells with DTT prior to HQ administration protected cells against HQ-induced toxicity. DTT induced QR activity in a dose-dependent manner in stromal cells from both strains of mice. However, there were no corresponding changes in glutathione transferase activity. DTT also increased cytosolic glutathione (GSH) concentrations by approximately 85% in both strains. Since bone marrow stroma consists primarily of fibroblasts and macrophages, we also evaluated QR activity in the separate cell types from the two strains of mice. There were differences in basal and DTT-induced QR activity between fibroblasts and macrophage cells derived from the same strain of mice, as well as the expected differences between strains. Additionally, dicoumarol, an inhibitor of QR activity, potentiated HQ-induced toxicity in both strains of bone marrow stromal cells. Thus, cellular glutathione, QR activity, and their inducibility by chemoprotective agents such as DTT may prove to be important factors in chemically induced bone marrow toxicity and carcinogenicity.
...
PMID:Induction of quinone reductase and glutathione in bone marrow cells by 1,2-dithiole-3-thione: effect on hydroquinone-induced cytotoxicity. 137 15

Each of the four stereoisomers of trans-3,4-dihydroxy 1,2-epoxy 1,2,3,4-tetrahydrobenzo[c]phenanthrene [(+)- and (-)-anti-BPhDE and (+)- and (-)-syn-BPhDE] has been incubated with the human glutathione transferase (GST) isoenzymes GST A1-1, GST M1-1 and GST P1-1, representing class alpha, mu and pi respectively, and glutathione (GSH). The conjugates formed were analyzed by HPLC and the results demonstrate that all GST isoenzymes catalyze the formation of GSH conjugates of all BPhDE isomers. However, a marked variation in catalytic efficiencies was observed (0.122-1.28/mM/s). These values are considerably lower than those previously estimated for the bay-region diol epoxides of benzo[a]pyrene (B[a]P) and human GSTs. The (+)-syn and (-)-anti-BPhDE (1R,2S-epoxide absolute configuration) were in general better substrates than the corresponding 1S,2R-epoxides. In accordance with previous observations with the diolepoxides of B[a]P, GST P1-1 was highly selective towards the BPhDE isomer with 4R,3S-diol 2S,1R-epoxide absolute configuration, i.e. (-)-anti-BPhDE, whereas GST A1-1 and M1-1 preferentially catalyzed the conjugation of (+)-syn-BPhDE (4R,3S-diol 2R,1S-epoxide absolute configuration). Overall, the most active isoenzyme was GST A1-1. Analysis by NMR spectroscopy of the GSH conjugates of BPhDE demonstrate that the reaction with GSH generally takes place by trans-addition of the thiol group at the benzylic C-1 carbon. The low catalytic efficiencies of human GSTs with BPhDE as compared to diolepoxides of B[a]P may be explained in part by the more crowded bay-region and substantially lower chemical reactivity (e.g. delta Edeloc/beta) of the former compounds.
...
PMID:Glutathione conjugation of trans-3,4-dihydroxy 1,2-epoxy 1,2,3,4-tetrahydrobenzo[c]phenanthrene isomers by human glutathione transferases. 139 38

The influence of oleic, linoleic (LIN), and eicosapentaenoic (EPA) acids incorporated into cellular lipids on susceptibility to O2-induced toxicity was evaluated in Chinese hamster fibroblasts (HA1) using a clonogenic cell survival assay. Fatty acid incorporation was achieved by incubating HA1 cells in 21% O2 for 72 h in the presence or absence of media supplemented with 25 microM oleic acid, 25 microM LIN, or 2, 4, and 25 microM EPA. This fatty acid incorporation period increased the percentage of composition in phospholipids 2-fold for oleic acid, 6-fold for LIN, and 6- to 20-fold for EPA. Vitamin E, total glutathione, superoxide dismutase activity, glutathione transferase activity, and catalase activity were unchanged, relative to control, in the 25-microM EPA-treated group, and only total glutathione was elevated in the LIN-treated group. After the incorporation period, the cells were placed in non-fatty acid supplemented media and exposed to 95% O2, and clonogenic survival responses were evaluated at time intervals up to 100 h. Sensitization to O2 toxicity in EPA-treated cells was apparent after 24 h of O2 exposure, whereas LIN-treated cells were significantly (p less than 0.05) sensitized to hyperoxia after 54 h of exposure, indicating that EPA was a more potent sensitizer for O2 injury. Furthermore, cells supplemented with 4 and 25 microM EPA were more sensitive to O2 toxicity than cells supplemented with 2 microM EPA. In contrast, cells treated with 25 microM oleic acid were significantly more resistant to O2 toxicity at 51, 72, and 98 h of O2 exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:The effect of monosaturated and polyunsaturated fatty acids on oxygen toxicity in cultured cells. 140 77

Three reactions (nucleophile substitution, thiolysis and N-deoxygenation) catalyzed by rat liver glutathione transferase have been studied using several N-heterylazimine inhibitors. The inhibitors are sharply different in their effectiveness in the transferase reactions. Their efficiency depends on their structure. The mechanism which underlies the found regularities is suggested.
...
PMID:[Selective N-heterylazimine inhibition of reactions catalyzed by rat liver glutathione transferase]. 141 25

Male mice were exposed via their diet to perfluoro fatty acids of various chain-lengths (2-10 carbon atoms) at different doses (0.02 and 0.1% weight) and for different periods of time (2-10 days). Thereafter, we monitored effects on liver and body weights and a number of hepatic parameters, including mitochondrial protein content, microsomal contents of cytochromes P450 and b5, NADPH-cytochrome P450 reductase activity [measured as NADPH-cytochrome c reductase (EC 1.6.2.3)], microsomal and cytosolic epoxide hydrolase (EC 3.3.2.3) activities, cytosolic DT-diaphorase (EC 1.6.99.2), glutathione transferase (EC 2.5.1.18), glutathione peroxidase (EC 1.11.1.9) and superoxide dismutase (EC 1.15.1.1) activities, and levels of thiobarbituric acid-reactive material (as an indicator of lipid peroxidation) in the mitochondrial subfraction. The most dramatic changes observed were a 5-9-fold increase in mitochondrial protein, a 3-6-fold increase in the microsomal content of cytochrome P450, a 3-10-fold increase in cytosolic DT-diaphorase activity, an approximately 2-fold increase in cytosolic epoxide hydrolase activity and as much as a 60% decrease in the level of thiobarbituric acid-reactive compounds in the mitochondrial fraction. Smaller increases in microsomal epoxide hydrolase activity and decreases in cytosolic glutathione peroxidase activity were also observed. Of the perfluoro fatty acids tested, perfluorooctanoic acid caused the largest changes in the parameters examined here. Dietary exposure of mice to a 0.02% dose of this substance for 10 days results in a maximal or near-maximal effect in most cases.
...
PMID:Effects of perfluoro fatty acids on xenobiotic-metabolizing enzymes, enzymes which detoxify reactive forms of oxygen and lipid peroxidation in mouse liver. 141 40

Changes in pro-oxidant and antioxidant balance in the serum and liver were studied in an experimental model of obstructive jaundice in the rat. The results showed a decrease in plasma vitamin E concentration (P < 0.01) and a threefold reduction in liver vitamin E concentration (P < 0.001). There was also a threefold reduction in levels of the liver enzymes glutathione peroxidase (P < 0.01) and glutathione transferase (P < 0.001), together with a six-fold reduction in catalase activity (P < 0.001). The serum selenium level decreased by 35% in the jaundiced rats (P < 0.05). The total liver glutathione level decreased to half the control value (P < 0.01). The malonyldialdehyde level, the measure of lipid peroxidation used in this study, doubled (P < 0.01). The results suggest a shift in the pro-oxidant/antioxidant balance in favor of lipid peroxidation. The possible etiology of this change and its relationship to human cholestasis are discussed.
...
PMID:Antioxidant defenses in the bile duct-ligated rat. 142 83

Developmental profiles of the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), glutathione transferase (GSH-Tr), and hexose monophosphate shunt (HMS) were measured in the rat testis and liver. The level of SOD in the testis was high at the age of 6 to 10 days, after which it dropped to approximately one third of that level by 20 days of age, and remained there up to 8 months of age. In the liver, SOD activity steadily increased from the neonatal to adult stage of life, reaching the same level as detected in the testis. The testicular activity of catalase was only 2% to 7% of that found in liver at all ages. It increased in both organs up to 6 weeks of age, whereafter the hepatic activity gradually decreased and no further changes were seen in the testis. The GSH-Px activity was low in the testis and declined slightly with age, whereas activity in the liver increased four-fold between birth and adulthood. The activity of GSH-Tr was similar in both organs studied: it increased after birth, showing a maximum in the liver at 1.5 months (ten-fold increase) and in the testis at 5 months of age (four-fold increase). The HMS activity was two to three times higher in the liver than in the testis, and decreased slightly with age in both organs. Thus, the basal levels and developmental profiles of antioxidant enzymes in the testis differ greatly from those in the liver.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Antioxidant enzyme activity in the maturing rat testis. 142 21

The analysis of glutathione transferase (GST) isoenzyme patterns is of interest in many fields as hepatic glutathione transferase activity is increased by exposure to a variety of xenobiotics and its isoenzymatic forms are induced differentially. A high-performance liquid chromatography method has been developed for the rapid determination of individual isoenzyme levels in crude extracts using an anion-exchange column connected to an on-line system to automatically detect GST activity with 1-chloro-2,4-dinitrobenzene as the substrate. When 50-200 microliters of a cytosolic fraction of fish liver containing up to 15 mg/ml of protein and less than 2 units of GST were injected, a high resolution and highly reproducible chromatogram was obtained. The activity profile determined automatically showed eight to twelve peaks (depending on the sample) that were quantified and could be classified into three groups. Starting from intact tissue, a complete isoenzyme pattern could be obtained in less than 3 h. The method has been applied to ecotoxicological studies with fish samples.
...
PMID:Rapid method for the determination of glutathione transferase isoenzymes in crude extracts. 143 39


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---