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)

We demonstrate the possibility of automation of whole-cell functionality assays, e.g., mitogen-activated DNA synthesis, DNA repair synthesis, and assessment of drug-metabolizing enzymes, by use of magnetic separation technology. We have attached antibody-coupled magnetic microspheres to the surface of human T-lymphocytes before performing various assays. Evaluating the biological functions of T-cells estimated by the DNA-synthesis assays showed that the presence of antibody-coupled magnetic microspheres did not affect the results (P greater than 0.05). The concentration of adenosine diphosphate ribosyltransferase (EC 2.4.2.30) was shown to be influenced by the magnetic microspheres. However, the amount of enzyme activity induced by oxidative stress was not significantly altered. The results from assays of the phase II drug-metabolizing enzymes glutathione transferase (EC 2.5.1.18) and epoxide hydrolase (EC 3.3.2.3) as well as evaluation of the proliferative response of polyclonal activators (phytohemagglutinin, staphylococcal enterotoxin A, and pokeweed mitogen) support our conclusion that assays can be performed on viable magnetized cells. The use of magnetized cells holds promise for further applications in automated genotoxic and immunological cell assays of mononuclear leukocyte subsets. Laboratory robotics will be essential in bringing these assays into routine use.
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PMID:Magnetically tagged subsets of human lymphocytes for assays with laboratory robotics. 211 12

The effects of inhibitors of poly(ADP-ribose)polymerase, 3-aminobenzamide (ABA), luminol and 3-methoxybenzamide (MBA) on the rat liver tumor promotion activity of phenobarbital (PB) were assessed. Fischer 344 male rats were initiated with N-nitrosodiethylamine (200 mg/kg) and placed on either basal diet, diet containing 0.05% PB, diet containing various doses of the inhibitors alone or diet containing 0.05% PB plus various doses of inhibitors for 10 weeks, and then killed. Quantitation of the development of glutathione S-transferase placental form-positive foci revealed that ABA at doses of 2 and 1.5, but not 1%, significantly inhibited the PB promotion activity. Luminol dose-dependently reduced PB promotion at doses of 3 and 6% but exerted no effects at the 1 and 2% levels. MBA also demonstrated a dose-dependent inhibitory influence at doses of 1 and 2%. The results are thus strongly suggestive of an involvement of poly ADP-ribosylation in the mechanisms underlying liver tumor promotion by PB.
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PMID:Possible involvement of poly ADP-ribosylation in phenobarbital promotion of rat hepatocarcinogenesis. 211 7

Morphology, urinary enzyme excretion and mitochondrial function was studied in rats fed over a period of 30 days with 20 and 40 mg CsA/kg body weight. Already on day 8 vacuolisation and augmentation of autophagic vacuoles, lipid droplets and a loss in microvilli can be observed in the S-3 segment of the proximal nephron using the lower CsA dose. These effects are enhanced during the treatment period. The overall effect, however, is a subtle one. The dose of 40 mg/kg produces more pronounced cellular alterations, a more severe vacuolisation, but also focal prenecrotic damage of proximal tubular S-2 and S-3 cells. The cells altered in that manner amount to roughly 5% of the total proximal tubular epithelium. Enhanced urinary excretion of the proximal cytosolic enzymes, fructose-1,6-bisphosphatase, glutathione S-transferase, pyruvate kinase and the lysosomal N-acetyl-beta-D-glucosaminidase appear to parallel the morphologic changes, whereby only the excretion of pyruvate kinase is significantly elevated on day 30 using 40 mg/kg. Decrease in oxidative phosphorilation capacity (ADP:O ratio) was found with both CsA doses, however, this result seems to be dissociated from changes in morphology and enzyme excretion. Studies on isolated tubular fragments in vitro, exposed to CsA exhibited an inhibition of the cytosolic malate dehydrogenase isoenzyme, which could be interpreted as a possible source of the CsA induced tubular alteration.
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PMID:Morphological and biochemical observations in rat nephron epithelia following cyclosporine A (CsA) treatment. 301 36

A chemical plant, where an increased number of non-Hodgkin's lymphomas and myelomas had been observed, was monitored for genotoxic effects occurring in peripheral mononuclear leukocyte samples from 76 exposed workers. Biochemical markers sensitive to DNA repair and drug metabolism were used as the indicators of genotoxic risk. Unscheduled DNA synthesis (UDS) and covalent binding induced by N-acetoxy-N-acetyl-2-aminofluorene (NA-AAF) and constitutive and gamma ray induced adenosine diphosphate ribosyl transferase (ADPRT) activities were highly and significantly elevated over the corresponding values for a control group of 48 postal workers. Microsomal and soluble epoxide hydrolases and glutathione transferase activities directed towards trans-stilbene oxide and 1-chloro-2,4-dinitrobenzene were not significantly altered in the exposed group. The exposure in this factory was complex, involving over 100 chemicals including several well known carcinogens. However, no apparent significant associations to exposure could be established.
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PMID:Biological effects in a chemical factory with mutagenic exposure. II. Analysis of unscheduled DNA synthesis and adenosine diphosphate ribosyl transferase, epoxide hydrolase, and glutathione transferase in resting mononuclear leukocytes. 313 75

Lipid peroxidation has been found decreased in several hepatomas. The decline has been shown already at the level of preneoplastic nodules obtained after DEN treatment of rats. A substantial exception is represented by the hepatoma cell line MH1C1, deriving from a slightly deviated Morris tumor. Most of the described experiments estimated lipid peroxidation levels in terms of malonaldehyde production by the thiobarbituric acid test. It is now clear that this test does not account for several other aldehydes produced during lipid peroxidation. We now investigated by high performance liquid chromatography (HPLC) the whole range of non-polar aldehydes produced by tumor homogenates and by preneoplastic nodules both in basal conditions and after stimulation with ADP-iron or ascorbate. It was reduced in the preneoplastic nodules as well as in the DEN-induced hepatoma. The susceptibility to the prooxidant effect of ADP-iron or ascorbate was strongly decreased in all hepatomas as well as in preneoplastic nodules. It has been recently published that hepatoma cells are more susceptible than normal liver to the toxic action of aldehydes. This was attributed at least in part to the decreased activity of aldehyde dehydrogenases, as well as to their different distribution in tumor cells. A deeper study on aldehyde metabolism in hepatomas has shown that alcohol dehydrogenase and NADPH-aldehyde reductase also are markedly decreased in Yoshida hepatoma cells and the MH1C1 cell line. However, glutathione transferase, that can use hydroxynonenal as a substrate, is strongly decreased in Yoshida hepatoma cells but not in MH1C1 cells.
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PMID:New data on kinetics of lipid peroxidation in experimental hepatomas and preneoplastic nodules. 380 93

The peroxisome proliferators perfluorooctanoic acid (PFOA; 0.02% w/w), perfluorodecanoic acid (PFDA; 0.02%, w/w), nafenopin (0.125%, w/w), clofibrate (0.5%, w/w), and acetylsalicylic acid (ASA; 1%, w/w) were administered to male C57 BL/6 mice in their diet for two weeks. Parameters for Fe3+ ADP, NADPH or ascorbic acid-initiated lipid peroxidation in vitro were measured. Approximately a twofold increase in susceptibility to lipid peroxidation was obtained for all the peroxisome proliferators tested. Cotreatment of mice with the peroxisome proliferator ASA (1%, w/w) and a catalase inhibitor, 3-amino-1,2,4-triazole (AT; 0.4%, w/w) for 7 days resulted in little inhibition of peroxisome proliferation, an elevated level of H2O2 in vivo, and total inhibition of the increased susceptibility to lipid peroxidation in vitro. No increase in lipid peroxidation in vivo was observed. Certain antioxidant enzymes (DT-diaphorase, superoxide dismutase, glutathione transferase, glutathione peroxidase, and glutathione reductase) and components (ubiquinone and alpha-tocopherol) were also measured. The results showed that there was some induction of these antioxidant enzymes and components by ASA or aminotriazole, except for glutathione peroxidase and superoxide dismutase, which were inhibited. The possible involvement of oxidative stress in the carcinogenicity of peroxisome proliferators is discussed.
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PMID:Hepatic oxidative stress and related defenses during treatment of mice with acetylsalicylic acid and other peroxisome proliferators. 756 57

An activator of rat brain phospholipase D (PLD) that is distinct from the already identified PLD activator, ADP-ribosylation factor (ARF), was partially purified from bovine brain cytosol by a series of chromatographic steps. The partially purified preparation contained a 22-kDa substrate for Clostridium botulinum C3 exoenzyme ADP-ribosyltransferase, which strongly reacted with anti-rhoA p21 antibody, but not with anti-rac1 p21 or anti-cdc42Hs p21 antibody. Treatment of the partially purified PLD-activating factor with both C3 exoenzyme and NAD significantly inhibited the PLD-stimulating activity. These results suggest that rhoA p21 is, at least in part, responsible for the PLD-stimulating activity in the preparation. Recombinant isoprenylated rhoA p21 expressed in and purified from Sf9 cells activated rat brain PLD in a concentration- and GTP gamma S (guanosine 5'-O-(3-thiotriphosphate))-dependent manner. In contrast, recombinant non-isoprenylated rhoA p21 (fused to glutathione S-transferase) expressed in Escherichia coli failed to activate the PLD. This difference cannot be explained by a lower affinity of non-isoprenylated rhoA p21 for GTP gamma S, as the rates of [35S]GTP gamma S binding were very similar for both recombinant preparations and the GTP gamma S-bound form of non-isoprenylated rhoA p21 did not induce PLD activation. Interestingly, recombinant isoprenylated rhoA p21 and ARF synergistically activated rat brain PLD; a similar pattern was seen with the partially purified PLD-activating factor. The synergistic activation was inhibited by C3 exoenzyme-catalyzed ADP-ribosylation of recombinant isoprenylated rhoA p21 in a NAD-dependent manner. Inhibition correlated with the extent of ADP-ribosylation. These findings suggest that rhoA p21 regulates rat brain PLD in concert with ARF, and that isoprenylation of rhoA p21 is essential for PLD regulation in vitro.
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PMID:Synergistic activation of rat brain phospholipase D by ADP-ribosylation factor and rhoA p21, and its inhibition by Clostridium botulinum C3 exoenzyme. 759 44

The motor protein non-claret disjunctional (ncd) moves towards the minus ends of microtubules (MTs), whereas its close relative kinesin moves in the opposite direction towards the plus ends of MTs. The mechanisms of movement and directional reversal for these motor proteins are unknown. Here we report the rate constants for MT activated ADP release from a recombinant double-headed ncd protein, GST-MC5, and a recombinant double-headed kinesin protein, K delta 401, measured using the fluorescent nucleotide analogues methylanthranilyol ATP (mantATP) and mantADP. Comparison of the maximal MT activated mantADP release rates for these proteins with their maximal MT activated mantATP turnover rates indicates that ADP release is the rate-limiting step for ATP turnover for both ncd and kinesin. This data supports the view that directional reversal may result from structural rather than chemical kinetic differences in the way the motors interact with MTs.
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PMID:ADP release is the rate-limiting step of the MT activated ATPase of non-claret disjunctional and kinesin. 763 15

The ability of the benzoquinone coenzyme Q-10 or its derivative QSA-10 (idebenone) to protect against lipid peroxidation and protein damage mediated by the pro-oxidative system NADPH/ADP/Fe3+ was tested in a rat liver microsomal model incubated in University of Wisconsin (UW) or histidine-tryptophan-ketoglutarate (HTK) solutions. Lipid peroxidation, as followed by direct determination of lipid hydroperoxides and by monitoring of malondialdehyde equivalents, was 1.8-fold enhanced in HTK and 3-fold attenuated in UW compared with HEPES buffer. Function and integrity of microsomal enzymes were investigated using glutathione S-transferase and cytochrome P-450 IIIA activity as assessed by lidocaine N-deethylation to monoethylglycinexylidide as well as by Western blot analysis of the cytochrome P-450 IIIA protein. Glutathione S-transferase activity was reduced by about 70% in HEPES compared with 50% in HTK and 36% in UW. Cytochrome P-450 IIIA was inactivated by about 75% in HEPES and HTK, compared with 55% in UW. The enzyme inactivation was paralleled by a loss of immunoreactive cytochrome P-450 IIIA protein. Supplementation of HTK with 0.1 mumol/L QSA-10 offered complete protection against lipid peroxidation, compared with 100 mumol/L with Q-10. QSA-10 (20 mumol/L) prevented protein damage in both preservation solutions, whereas Q-10 (20 mumol/L) offered only partial protection in UW and had no effect in HTK. The use of QSA-10 during liver transplantation may therefore have the potential of increasing the efficacy of organ preservation, maintaining donor organ quality, and preventing reperfusion injury. It is suitable for human use and has energy-conserving properties in addition to its antioxidant nature.
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PMID:Idebenone protects hepatic microsomes against oxygen radical-mediated damage in organ preservation solutions. 767 91

We have identified a 70-kDa cytosolic protein (GTBP70) in rat adipocytes that binds to glutathione S-transferase fusion proteins corresponding to the cytoplasmic domains of the facilitative glucose transporter isoforms Glut1, Glut2, and Glut4. GTBP70 did not bind to irrelevant fusion proteins, indicating that the binding is specific to the glucose transporter. GTBP70 binding to the glucose transporter showed little isoform specificity but was significantly subdomain-specific; it bound to the C-terminal domain and the central loop, but not to the N-terminal domain of Glut4. The GTBP70 binding to Glut4 was not affected by the presence of 2 mM EDTA, 2.4 mM Ca2+, or 150 mM K+. The binding was inhibited by ATP in a dose-dependent manner, with 50% inhibition at 10 mM ATP. This inhibition was specific to ATP, as ADP and AMP-PCP (adenosine 5'-(beta, gamma-methylenetriphosphate)) were without effect. GTBP70 did not react with antibodies against phosphotyrosine, phosphothreonine, or phosphoserine, suggesting that it is not a phosphoprotein. The binding of GTBP70 to Glut4 was not affected by the pretreatment of adipocytes with insulin. When these experiments were repeated using rat hepatocyte cytosols, no ATP-sensitive 70-kDa protein binding to the glucose transporter fusion proteins was evident, suggesting that either GTBP70 expression or its function is cell-specific. These findings strongly suggest the possibility that GTBP70 may play a key role in glucose transporter regulation in insulin target cells such as adipocytes.
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PMID:ATP-sensitive binding of a 70-kDa cytosolic protein to the glucose transporter in rat adipocytes. 771 80


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