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)

The reduction of linoleic acid hydroperoxide catalysed by rat liver cytosol was previously shown to be catalysed by a selenium-dependent glutathione peroxidase. In contrast, the enzyme responsible in guinea-pig liver cytosol is not selenium-dependent and appears to be a glutathione transferase.
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PMID:Lipid and steroid hydroperoxides as substrates for the non-selenium-dependent glutathione peroxidase. 43 67

There are two enzymes in rat liver with glutathione peroxidase activity when cumene hydroperoxide is used as substrate. One is the selenium-requiring glutathione peroxidase (glutathione:hydrogen-peroxide oxidoreductase, EC 1.11.1.9) and the other appears to be independent of dietary selenium. Activities of the two enzymes vary greatly among tissues and among animals. The molecular weight of the enzyme with selenium-independent glutathione peroxidase activity was estimated by gel filtration to be 35 000, and the subunit molecular weight was estimated by dodecyl sulfate-polyacrylamide gel electrophoresis to be 17 000. Double reciprocal plots of enzyme activity as a function of substrate concentration produced intersecting lines which are suggestive of a sequential reaction mechanism. The Km for glutathione was 0.20 mM and the Km for cumene hydroperoxide was 0.57 mM. The enzyme was inhibited by N-ethylmaleimide, but not by iodoacetic acid. Inhibition by cyanide was competitive with respect to glutathione and the Ki for cyanide was 0.95 mM. This selenium-independent glutathione peroxidase also catalyzes the conjugation of glutathione to 1-chloro-2,4-dinitrobenzene. Along with other similarities to glutathione S-transferase, this suggests that the selenium-independent glutathione peroxidase and glutathione S-transferase activities in rat liver are of the same enzyme.
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PMID:Glutathione peroxidase activities from rat liver. 62 91

Recent work had indicated the presence of a non selenium-dependent glutathione peroxidase activity in rat liver in addition to the selenium-dependent activity. The present study was undertaken to learn whether the glutathione S-transferases are reponsible for the non selenium-dependent glutathione peroxidase activity and to study the effect of selenium deficiency on those enzymes. Glutathione S-transferase B was purified by an established method using carboxymethyl cellulose ion exchange chromatography and studied. It exhibited glutathione peroxidase activity toward cumene hydroperoxide and t-butyl hydroperoxide. A limiting Km of 0.55 mM was determined for cumene hydroperoxide. Sulfobromophthalein was found to be a competitive inhibitor with respect to cumene hydroperoxide of the glutathione peroxidase activity of glutathione S-transferase B. Selenium deficiency caused an increase in glutathione S-transferase activity. These results establish that glutathione S-transferase B contributes to the non selenium-dependent glutathione peroxidase activity in rat liver and show that it increases in selenium deficiency when the selenium-dependent glutathione peroxidase is decreased.
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PMID:Hepatic cytosolic non selenium-dependent glutathione peroxidase activity: its nature and the effect of selenium deficiency. 65 Mar

Cytotoxicity of Adriamycin on human colon adenocarcinoma cell lines was investigated. Concentrations of Adriamycin producing 50% inhibition were very similar in HT29, Sw480, Sw620, and Sw1116 cells, whereas Caco-2 cells were relatively insensitive. As compared to the Sw1116 cell line, Caco-2 cells were also insensitive to mitoxantrone. Sensitivity to cisplatin, 5-fluorouracil, or ethacrynic acid was comparable in both cell lines. To find the mechanism for this mitoxantrone and Adriamycin resistance, several potential Adriamycin-detoxifying systems were characterized and quantified in both Sw1116 and Caco-2 cells. No dramatic differences in glutathione content and expression of both selenium dependent- and independent glutathione peroxidase, UDP-glucuronyltransferase, and cytochrome P-450 were found. However, highly significant differences in glutathione S-transferase activity were present, the expression of both class pi and class alpha glutathione S-transferases being much higher in the Caco-2 cell line. In addition, a slightly higher content of P-170 glycoprotein was present in the Caco-2 cells. These findings suggest that glutathione S-transferases, and to a lesser extent the P-170 glycoprotein, may be involved in mitoxantrone and Adriamycin resistance of Caco-2 colon carcinoma cells.
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PMID:Biochemical characterization of resistance to mitoxantrone and adriamycin in Caco-2 human colon adenocarcinoma cells: a possible role for glutathione S-transferases. 134 15

Since human colorectal tumors are insensitive to most chemotherapeutic agents, there is a need for the discovery of new drugs that would show activity against this disease. In an attempt to better appreciate the relevance of a widely used mouse colon tumor (colon adenocarcinoma Co38) as a screening model for human colorectal tumors, we compared the main phase I and phase II drug-metabolizing enzyme systems in both tumoral and nontumoral colon tissues. The following enzymes were assayed by Western blot: cytochromes P-450 (1A1/A2, 2B1/B2, 2C, 2E1, and 3A), epoxide hydrolase, and glutathione-S-transferases (GST-alpha, -mu, and -pi). The activities of the following enzymes or cofactors were determined by spectrophotometric or fluorometric assays: total cytochrome P-450, 1-chloro-2,4-dinitrobenzene-GST, selenium-independent glutathione peroxidase, 3,4-dichloronitrobenzene-GST, ethacrynic acid-GST, total glutathione, epoxide hydrolase, UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, and sulfatase. Results obtained by Western blot showed that mouse colon adenocarcinoma Co38 did not express any of the probed cytochromes P-450, whereas human colorectal tumors expressed only low levels of cytochrome P-450 3A. GST-alpha and GST-pi were detected in all tumoral and nontumoral tissues of both species. The neutral GST-mu was expressed in all murine tissues investigated and was found to be polymorphic in human tissues. For human peritumoral and tumoral colorectal tissues there was no significant difference between GST isoenzyme levels, whereas mouse colon adenocarcinoma Co38 had a lower expression of GST-mu and GST-pi, compared to normal mouse colon. Enzymatic activities for glutathione peroxidase, 3,4-dichloronitrobenzene-GST, and ethacrynic acid-GST confirmed the Western blot results for GST-alpha, GST-mu, and GST-pi, respectively. Total GSH levels were similar between murine and human tumors but were 3-fold higher in human tumors than in peritumoral tissues, whereas they were 7-fold lower in mouse colon tumor Co38, compared to normal mouse colon. Epoxide hydrolase was not expressed in either mouse colon adenocarcinoma Co38 or normal mouse colon tissues, whereas it was expressed in human colon peritumoral and tumoral tissues at similar levels. No significant difference was observed between human tumors and peritumoral tissues for UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, and sulfatase. For murine colon tissues, the conjugation pathways (UDP-glucuronosyltransferase and sulfotransferase) were lower in colon adenocarcinoma Co38, whereas the converse was observed for the corresponding hydrolytic enzymes (beta-glucuronidase and sulfatase).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparison of mouse and human colon tumors with regard to phase I and phase II drug-metabolizing enzyme systems. 142 2

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.
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PMID:Antioxidant defenses in the bile duct-ligated rat. 142 83

Circadian variations in antioxidant defences and lipid peroxidation were investigated in 12 rat hearts perfused during light (i.e., at 08.00, n = 6) and dark cycle (i.e., at 19.00, n = 6). Higher levels of non proteic thiol compounds (P < 0.01), glutathione transferase activity (P < 0.05) and lipid peroxidation (P < 0.01) were detected in evening-excised hearts, associated with a lower (P < 0.05) selenium-dependent glutathione peroxidase activity; superoxide dismutase and glutathione reductase activities, as well as vitamin E content, were similar in the two groups. Moreover, a greater release of thiobarbituric acid reactive substances (P < 0.01) and proteins (P < 0.05) was detected in the myocardial effluent of another group of 5 evening-excised hearts perfused with Krebs-Henseleit buffer containing 30 microM cumene hydroperoxide, as compared to 5 light-cycle hearts. In conclusion, a higher oxidative stress seems to be operative in the rat heart during early stages of the dark phase, in spite of the increase level of non proteic thiol compounds (namely, glutathione). An imbalance of antioxidant defences, and/or higher radical generation and unsaturation degree of biomembranes lipids, may be hypothesized to favour myocardial oxidative stress at the beginning of the motor activity phase in rats.
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PMID:Circadian variations in antioxidant defences and lipid peroxidation in the rat heart. 145 91

In 7 rabbits fed on hyperlipidic diet (0.5% cholesterol, 5% peanut oil and 5% lard) for 4 weeks, the ventricular myocardium was tested for antioxidant defences and thiobarbituric acid reactive substances. Seven age-matched rabbits served as controls. The hearts were previously subjected to 45 min Langendorff perfusion to study coronary flow, developed tension and resting tension; coronary effluent values of CPK activity, pH and UV absorbance at 250 nm (i.e., low molecular weight ATP catabolites) were also investigated. After 4 weeks of diet, a significant rise of plasma cholesterol (P < 0.0001) and triglycerides (P < 0.0001) was observed. Total superoxide dismutase, catalase and glutathione transferase activities underwent a significant increase (P < 0.05) in the hyperlipidemic animals. On the contrary, a depression of glutathione reductase (P < 0.01) and selenium-dependent glutathione peroxidase (P < 0.01) activities, associated with decreased levels of non proteic thiol compounds (P < 0.01), was assessed. The selenium-independent glutathione peroxidase activity was not detectable in both groups. Thiobarbituric acid reactive substances levels were significantly increased in the hyperlipidemic rabbit myocardium (P < 0.01). Even though heart hemodynamics, CPK release and perfusate pH did not differ in control and experimental animals, higher 250 nm absorbance values (P < 0.05) were detected in the myocardial effluent of hyperlipidemic rabbits. In conclusion, high fat-, cholesterol-enriched diet induces an imbalance in the rabbit heart antioxidant defences, some of which are increased, whereas others are depressed, eventually resulting in enhanced myocardial lipid peroxidation. These biochemical changes are associated with higher perfusate values of UV absorbance at 250 nm, but not with significant CPK leakage or myocardial hemodynamics derangement.
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PMID:Effects of high fat-, cholesterol-enriched diet on the antioxidant defence mechanisms in the rabbit heart. 146 87

The glutathione transferases (GSTs) comprise a family of enzymes that catalyze the conjugation of glutathione with certain hydrophobic compounds, bind various hydrophobic compounds, and have selenium-independent glutathione peroxidase activity. Of the four classes of GST, the pi class is the only one present in keratinocytes, and pi-class GST is elevated in psoriatic epidermis. We have purified and characterized GST from psoriatic scales. Immunoreactivity was observed with pi class antisera, and amino terminal sequencing showed identity with GST from human placenta and cultured human keratinocytes. We conclude that the majority of GST activity in psoriatic skin is due to a pi-class isoenzyme, and pi-class GST may represent an index for hyperproliferation.
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PMID:Purification and characterization of glutathione transferase from psoriatic skin. 147 89

Influences of dietary selenium (Se) deficiency, physical training and an acute bout of exercise on myocardial antioxidant enzyme activity, lipid peroxidation and related biochemical properties were investigated in post-weanling male Sprague-Dawley rats. An experimental group was fed a diet containing less than 0.01 mg Se/kg and had free access to distilled water (Se-D), whereas control rats were supplemented with 0.5 mg Se/l in drinking water (Se-A). Se deficiency depleted heart mitochondrial and cytosolic Se-dependent glutathione peroxidase activity to 24 and 3%, respectively, of those in Se-A rats. Heart mitochondrial superoxide dismutase (Mn SOD) activity was 24% higher (p less than 0.05) in Se-D than in Se-A rats. Cytosolic (copper-zinc) SOD and catalase activities were not altered, whereas glutathione S-transferase activity was significantly decreased in Se-D (p less than 0.01). Myocardial antioxidant enzyme activities were not affected by either training or an acute exercise bout. Heart lipid peroxidation and activities of several enzymes in substrate metabolism were also unaffected by Se or exercise. It is concluded that rat heart has sufficient reserve of antioxidant enzyme capacity in coping with oxidative stress imposed by Se deficiency or exercise. The adaptation of Mn SOD may reveal its potential role in myocardial antioxidant defense.
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PMID:Antioxidant enzyme response to selenium deficiency in rat myocardium. 153 41


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