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 potential usefulness of an insect model to evaluate oxidative stress induced by environmental pollutants was examined with trivalent arsenic (As3+, NaAsO2) and pentavalent arsenic (As5+, Na2HAsO4) in adult female house flies, Musca domestica, and fourth-instar cabbage loopers, Trichoplusia ni. M. domestica was highly susceptible to both forms of arsenic following 48 h exposure in the drinking water with LC50s of 0.008 and 0.011% w/v for As3+ and As5+, respectively. T. ni larvae were susceptible to dietary As3+ with an LC50 of 0.032% w/w but seem to tolerate As5+ well with an LC50 of 0.794% concentration after 48 h exposure. The minimally acute LC5 dose of both As3+ and As5+ varied considerably but averaged 0.005% for both insects. The potential of both valencies of arsenic for inducing oxidative stress in the insects exposed ad libitum to approximately LC5 levels was assessed. The parameters examined were the alterations of the antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione transferase (GST), the peroxidase activity of glutathione transferase (GSTPX), and glutathione reductase (GR), and increases in lipid peroxidation and protein oxidation. SOD (1.3-fold), GST (1.6-fold), and GR (1.5-fold) were induced by As3+ in M. domestica but CAT and GSTPX were not affected. As5+ had no effect on M. domestica. In T. ni, the antioxidant enzyme activities were not affected by As3+ except for SOD which was suppressed by 29.4% and GST which was induced by 1.4-fold. As5+ had no effect except the suppression of SOD by 41.2%. Lipid peroxidation and protein oxidation, which represent stronger indices of oxidative stress, were elevated in both insects by up to 2.9-fold. However, based on the antioxidant enzyme response to the arsenic anions, the mode of action of arsenic induced oxidative stress may differ between the two insects. Until this aspect is further clarified, evidence at this time favors the prospect of As3+ as a pro-oxidant, especially for M. domestica.
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PMID:An insect model for assessing oxidative stress related to arsenic toxicity. 760 44

Experiments were conducted to determine whether the increased glutathione S-transferase (GSH-T) activity associated with selenium (Se) deficiency is necessarily related to losses in the activity of Se-dependent glutathione peroxidase (SeGSHpx) in chicks. Nutritional Se status was altered in two ways: by treatment with an antagonist of Se utilization, aurothioglucose (AuTG), and by feeding diets containing excess Se. Chicks given AuTG (10-30 mg AU/kg, sc) had growth rates and hepatic GSH concentrations that were comparable to those of saline-treated controls; however, their plasma GSH levels exceeded those of either Se-deficient (6-fold) or -adequate (3-fold) saline-treated chicks. Hepatic SeGSHpx activities of AuTG-treated chicks were half those of controls under conditions of Se-adequacy; however, this effect was not detected when Se was deficient. Hepatic GSH-TCDNB (assayed with 1-chloro-2,4-dinitrobenzene) activities of AuTG-treated chicks were significantly greater than those of controls when Se was deficient (i.e., when SeGSHpx activity was 12% of the Se-adequate level); however, deprivation of Se did not affect GSH-TCDNB activity in the absence of AuTG. Chicks fed excess Se (6-20 ppm as Na2SeO3) in diets containing either low (2 IU/kg) or adequate (100 IU/kg) VE, showed hepatic GSH-TCDNB activities and GSH concentrations greater than those of Se-adequate (0.2 ppm Se) chicks by 100% and 40%, respectively. That increased hepatic GSH-TCDNB activity can occur because of either AuTG or excess Se status under conditions wherein SeGSHpx activity is not affected indicates that the transferase response is not directly related to changes in the peroxidase.
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PMID:Effects of aurothioglucose and dietary Se on glutathione S-transferase activities and glutathione concentrations in chick tissues. 768 30

The Drosophila glutathione S-transferase D27 (GST D27) has been purified and characterized after direct expression of the intronless gstD27 gene in E. coli. The GST D27 has both conjugation activity against the common substrate 1-chloro-2,4-dinitrobenzene and peroxidase activity against cumene hydroperoxide. Its pH optimum is 8.5 in 0.125 M bis-tris propane buffer at 22 degrees C. It is more thermal labile than the human GST121. The GST D27 has two tyrosines at positions 3 and 4. Both of them appear to be important but neither of them is essential for the enzyme activity. Thus, other residues may also participate in catalysis. The two tyrosines of GST D27 could also be important in binding to GSH or S-hexyl GSH. Results from in vitro biochemical analyses were confirmed by the in vivo activity-based CDNB growth inhibition analyses. Our results clearly indicate that the Drosophila GST D isozymes are different from any of the known mammalian GSTs.
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PMID:Drosophila glutathione S-transferase D27: functional analysis of two consecutive tyrosines near the N-terminus. 772 54

The occurrence of inflammatory processes and of cancer in the human respiratory tract is intimately associated. One of the major factors in this is probably the recruitment of and stimulated activity of polymorphonuclear leukocytes (PML) in conjunction with the ability of these cells to convert various carcinogens to their ultimate active metabolites. In this study, we demonstrate that nitrite and sulfite, the major dissolution products of the environmental pollutants nitrogen dioxide and sulfur dioxide in water enhance the metabolic activation of trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-dihydrodiol), the proximal carcinogen of benzo[a]pyrene, to trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and tetraols, the corresponding hydrolysis products, in human PML prestimulated with 12-O-tetradecanoylphorbol-13-acetate. Nitrite was more efficient than sulfite in stimulating the formation of reactive intermediates of BP-7,8-dihydrodiol in PML that covalently bind to extracellular DNA and, in particular, to intracellular proteins. The mechanism by which sulfite stimulates the metabolism of BP-7,8-dihydrodiol most probably involves the intermediate formation of a sulfur trioxide radical anion (SO3.-) the subsequent formation of the corresponding sulfur peroxyl radical anion (.OOSO3-) in the presence of oxygen. The mechanism underlying the stimulatory action of nitrite is less clear but the major pathway seems to involve myeloperoxidase. These results offer an explanation for the increased incidence of lung cancer in cigarette smokers living in urban areas. The major glutathione transferase (GST) isoenzyme in human PML is GST P1-1, a Pi-class form. The GST activity of PML was found to be inversely correlated with the extent of binding of BP-7,8-dihydrodiol products to exogenous DNA. These results suggest that individuals exhibiting high GST-activity in the PML may be better protected against the type of carcinogenic dealt with in this study.
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PMID:Stimulatory effects of sulfur and nitrogen oxides on carcinogen activation in human polymorphonuclear leukocytes. 782 Dec 91

Recently, a mouse glutathione S-transferase (GST) isozyme, mGSTA4-4, which belongs to a distinct group of GSTs has been characterized in our laboratory. During the present studies, Western blot analyses of bovine ocular tissues using the antibodies raised against the recombinant mGSTA4-4 obtained by expression in Escherichia coli revealed that the orthologs of mGSTA4-4 were present in cornea, retina, iris-ciliary body and sclera, but absent in lens. These novel GST isozymes of bovine ocular tissues were purified by immunoaffinity chromatography using the antibodies against rec-mGSTA4-4 and were designated as bGST 5.8 (their pI value being 5.8). Amino acid sequences of CNBr fragments of bGST 5.8 from cornea, sclera, retina and iris-ciliary body showed high degree of primary structure homologies with the corresponding regions of mGSTA4-4 indicating these bovine GST isozymes were distinct from the alpha. mu and pi group GSTs and were the newest members of the group of GSTs to which mGSTA4-4 belongs. There were significant differences among the amino acid sequences of bGST 5.8 of cornea and iris-ciliary body and retina suggesting presence of at least two closely related genes at bGST 5.8 locus. bGST 5.8 isozymes showed high activity toward 4-HNE (four-to-five-fold higher than that towards 1-chloro-2,4-dinitrobenzene), expressed GSH-peroxidase activity towards fatty acid hydroperoxides and phospholipid hydroperoxides, and showed GSH-conjugating activity towards fatty acid epoxides suggesting that these isozymes may play an important role in protection mechanism against the endogenous toxicants formed during lipid peroxidation.
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PMID:A group of novel glutathione S-transferase isozymes showing high activity towards 4-hydroxy-2-nonenal are present in bovine ocular tissues. 783 4

Glutathione S-transferases have been partially characterised from the gastrointestinal nematode Heligmosomoides polygyrus. Two major subunit families were purified (24 and 23 kDa) with N-terminal homology to the mammalian Alpha family. Four dimeric forms of GST were purified from the nematode by glutathione-affinity chromatography, two major enzymes (pI 8.1, 5.0) and two minor forms (pI 5.8, 5.3). The purified GST pool could neutralize model and lipid peroxides via peroxidase activity but not peroxidation derived reactive carbonyls via glutathione transferase activity. Antisera raised to the pooled nematode GSTs appeared to recognize other Strongylida GSTs more strongly on Western blotting compared to mammalian GSTs.
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PMID:Glutathione S-transferases from the gastrointestinal nematode Heligmosomoides polygyrus and mammalian liver compared. 788 22

In the present study, we investigated the effects of high dietary fat on the growth of MX-1 heterotransplanted in athymic mice and its response to mitomycin C (MC) treatment. We found that high fat intake (25% corn oil, w/w) significantly increased tumor growth, but at the same time it also increased the tumor response to MC treatment compared to the control low fat diet (5% corn oil, w/w). In the tumors from mice fed either low (5% w/w) or high (25% w/w) fat, MC treatment induced oxidative challenge, indicated by significantly increased tumor total superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase peroxidase activities, as well as increased tumor lipid peroxidation. On the other hand, glutathione reductase activity was inhibited by MC treatment. Some of the enzymes which are known to activate MC, such as cytochrome b5 reductase and DT-diaphorase, were also induced in the tumor by high dietary fat intake. The enzyme activities in hepatic tissues were also altered by dietary fat and MC treatment but to a lesser extent. We conclude that high dietary fat intake could enhance the chemotherapeutic effect of MC by increasing MC-activating enzyme activities. The observed increase in lipid peroxidation after MC treatment in MX-1 human mammary carcinoma implanted in the nude mice could result from the observed inhibited glutathione reductase activity. It is tempting to speculate that this might be another antineoplastic mechanism for MC in addition to its known role as a bioreductive alkylating agent. Alternatively, glutathione reductase may be a target for bioreductive alkylation.
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PMID:Enhancement of the antineoplastic effect of mitomycin C by dietary fat. 798 42

It is well known that reperfusion damage of ischemic myocardium may be attributed to alterations in the antioxidant defense system against free radical aggression. In addition, the degree of myocardial damage may depend on the duration and severity of ischemia that precedes reperfusion. We carried out serial ischemic experiments (10, 30, 60 and 120 min) in ex-vivo rat hearts followed by 30 min reperfusion and we assayed the glutathione-dependent enzymatic activities (selenium-dependent glutathione-peroxidase: GSH-Px; selenium-independent glutathione peroxidase: GST-Px; glutathione-transferase: GST and glutathione-reductase: GS-SG-Red), Catalase activity (CAT) and non-proteic thiol compounds (NP-SH) at the end of reperfusion. We found a significant reduction of NP-SH, GSH-Px and CAT in ischemic/reperfused hearts from 30 min on, while GST activity was increased. In addition, we observed the appearance of a selenium-independent glutathione peroxidase activity (GST-Px) belonging to the GST system. In conclusion, we found the longer the duration of ischemia the greater the inbalance between the myocardial antioxidant system especially the GST activation, suggesting in particular for GST-Px, a role in the control of the damage against oxygen toxicity during ischemia/reperfusion.
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PMID:Myocardial antioxidant defense mechanisms: time related changes after reperfusion of the ischemic rat heart. 801 40

A mouse glutathione S-transferase (GST) isozyme designated as GST 5.7 or mGSTA4-4 belongs to a distinct subclass of the alpha-class isozymes of GST. It is characterized by kinetic properties intermediate between the alpha- and pi-classes of GSTs. We have recently cloned and expressed this isozyme (rec-mGSTA4-4) in E. coli and have reported its complete primary sequence (Zimniak, P., et al. (1992) FEBS Lett., 313, 173-176). Using antibodies raised against the homogenous rec-mGSTA4-4 expressed in E. coli, we now demonstrate that an ortholog of this isozyme was selectively expressed in various human tissues. The human ortholog of mGST A4-4 purified from liver had a pI value of 5.8 and constituted approx. 1.7% of total GST protein of human liver. Similar to other alpha-class GSTs, the N-terminus of this isozyme (GST 5.8) was also blocked. CNBr digestion of the enzyme yielded two major fragments with M(r) values of 12 kDa and 6 kDa. The sequences of these two fragments showed identities in 16 out of 20 residues and 17 out of 20 residues with the corresponding sequences of its mouse ortholog (mGSTA4-4), and showed significant homologies with the rat and chicken orthologs, GST 8-8 and GST CL3. Human liver GST 5.8 showed more than an order of magnitude higher activity towards t-4-hydroxy-2-nonenal as compared to 1-chloro-2,4-dinitrobenzene. This isozyme also expressed glutathione-peroxidase activity towards fatty acid, as well as phospholipid hydroperoxides suggesting its role in protection mechanisms against the toxicants generated during lipid peroxidation. Western blot analysis of human tissues revealed that this GST isozyme was selectively expressed in human liver, pancreas, heart, brain and bladder tissues, but absent in lung, skeletal muscle, spleen and colon.
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PMID:A novel glutathione S-transferase isozyme similar to GST 8-8 of rat and mGSTA4-4 (GST 5.7) of mouse is selectively expressed in human tissues. 814 70

Hepatic mitochondria from different mammalian species contain varying levels of glutathione S-transferase (GST) activities. More than 70% of the activity detectable in the mouse liver mitochondria is associated with the soluble matrix. The mouse mitochondrial matrix GST was purified using a combination of (NH4)2SO4 fractionation, Sephadex gel filtration and affinity chromatography on glutathione (GSH) conjugated Sepharose. The purified GST comigrates with the mouse cytosolic MI (or alpha form), and exhibits an apparent molecular mass of 25 kD on sodium dodecyl sulfate-polyacrylamide gels. Polyclonal antibody to the purified mitochondrial GST cross-reacted with the similarly migrating cytosolic MI GST, suggesting extensive immunochemical relatedness between these two forms. As previously demonstrated for the cytosolic alpha form, the mitochondrial GST catalyzes aflatoxin B1-GSH conjugation (6.3 nmol/mg protein/min) and exhibits peroxidase activity (6.7 mumol/mg protein/min). The putative mitochondrial GST only in intact mitochondria, but not in sonic disrupted mitochondria, is resistant to proteolytic digestion with trypsin, demonstrating its intramitochondrial location. Isoelectric focusing on the flat bed polyacrylamide gel system resolves the mitochondrial GST into two distinct components with apparent pI of 9.9 and 9.7, both of which cross-react with polyclonal antibody to the mitochondrial GST. Under the identical conditions, the most cationic form of cytosolic GST cross-reacting intensely with the antibody resolves as a single component with an apparent pI of 9.4. Thus the mitochondrial GST resembles the alpha family of isoenzymes, though it appears to represent independent molecular species different from the cytosolic forms.
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PMID:Purification and characterization of a hepatic mitochondrial glutathione S-transferase exhibiting immunochemical relationship to the alpha-class of cytosolic isoenzymes. 816 Dec 25


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