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 activity of enzymes of the antioxidation system and the content of some lipid peroxidation products in the liver and thymus of irradiated (0.21 C/kg) rats have been investigated. Glutathione reductase and glutathione transferase activity in the liver and thymus of rats decreased during the first 24 h after irradiation. There was a phase change in the catalase activity during the initial postirradiation period. The content of malonic dialdehyde increased immediately after irradiation and somewhat decreased during the first 24 h. In 24 h, there observed a radiation-induced increase in the diene conjugate content in the liver and thymus of rats, against the background of low activity of such antioxidation system enzymes as glutathione transferase, glutathione reductase and catalase.
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PMID:[Activity of antioxidant system enzymes and lipid peroxidation product content in the liver and thymus of rats in the early stages of irradiation]. 149 13

It was suggested that increased Cu-Zn superoxide dismutase (SOD-1) might be involved in the various biological abnormalities found in Down's syndrome (DS) such as premature aging and Alzheimer-type neurological lesions. As a model system for testing this hypothesis we have developed two strains of transgenic mice carrying only one copy of the human SOD-1 gene. In the first strain (TG1), no expression has been found by northern blot analysis. The second strain (TG2) exhibited human SOD-1 mRNA and increased SOD-1 activity in the brain (1.93 fold), in the heart (1.69 fold), thymus (1.49 fold) and to a lesser extent in muscle (1.25 fold), liver (1.19 fold), kidney (1.18 fold), spleen (1.35 fold), lung (1.26 fold) and erythrocytes (1.09 fold). In this strain, increased SOD-1 activity in the brain did not induce modifications in the seleno-dependent glutathione peroxidase, glutathione reductase and glutathione S-transferase activities. In brain homogenates, we have focused our studies on Tau proteins which are known to be the major antigenic components of paired helical filaments (PHF), both in DS and Alzheimer's disease. Our results suggested that, in our experimental conditions, the overexpression of SOD-1 did not induce the modifications of Tau proteins similar to those seen during neurofibrillary degeneration.
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PMID:Expression of human Cu-Zn superoxide dismutase gene in transgenic mice: model for gene dosage effect in Down syndrome. 182 30

The induction of oxidation and conjugation enzymes, the scavenging of carcinogen electrophiles, and the inhibition of aflatoxin B1 (AFB1) activation were examined as possible mechanisms of anti-carcinogenesis by indole-3-carbinol (I3C). Liver microsomal 7-ethoxycoumarin O-deethylase and 7-ethoxyresorufin O-deethylase activities were not induced significantly in rainbow trout fed diets containing 500-2000 ppm I3C for 8 days compared to trout fed the control diet. Furthermore, no detectable changes in the specific contents of cytochrome P-450 isozymes LM2 and LM4b, as measured by Western-blotting and immunoquantitation, were found in liver microsomes following dietary I3C administration. Dietary I3C had no significant effect on liver microsomal uridine diphosphate-glucuronyl-transferase activity, measured using the substrates 1-naphthol and testosterone, or on cytosolic glutathione S-transferase activity, measured using the substrate styrene oxide. The ability of I3C or its acid reaction products (RXM; generated by the reaction of I3C with HCl) to act as scavengers for the direct alkylating agent AFB1-8,9-Cl2 was examined. Addition of I3C or RXM to in vitro incubations did not inhibit the covalent binding of AFB1-8,9-Cl2 to calf thymus DNA. Kinetic analyses of microsome-mediated binding of AFB1 to DNA in vitro indicated that RXM inhibited the metabolic activation of AFB1. RXM increased the apparent Km for the AFB1-DNA binding reaction without changing the associated Vmax; the apparent Km values at 0, 3.5, 35, and 350 microM RXM were 35, 38, 66, and 86 microM for trout liver microsomes. RXM also inhibited the activation of AFB1 by rat liver microsomes, but I3C was not an effective inhibitor against AFB1-DNA binding mediated by either rat or trout liver microsomes. The results of the present study indicate that inhibition of microsome-activated AFB1 binding to DNA by I3C products may be of significant importance in I3C inhibition of hepatocarcinogenesis in trout and other species. The inhibition of carcinogen activation by I3C is contrasted with the mechanism of anti-carcinogenesis by beta-naphthoflavone, which involves induction of xenobiotic metabolizing enzymes.
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PMID:Mechanisms of anti-carcinogenesis by indole-3-carbinol. Studies of enzyme induction, electrophile-scavenging, and inhibition of aflatoxin B1 activation. 210 94

The mutagenicity of 1,2-dibromoethane is highly dependent upon its conjugation to glutathione by the enzyme glutathione S-transferase. The conjugates thus formed can react with DNA and yield almost exclusively N7-guanyl adducts. We have synthesized the S-haloethyl conjugates of cysteine and glutathione, as well as selected methyl ester and N-acetyl derivatives, and compared them for ability to produce N7-guanyl adducts with calf thymus DNA. The cysteine compounds were found to be more reactive toward calf thymus DNA and yielded higher adduct levels than did the glutathione compounds. Adduct levels tended to be suppressed when there was a net charge on the compound and were not affected by substitution of bromine for chlorine, as expected for a mechanism known to involve an intermediate episulfonium ion. Sequence-selective alkylation of fragments of pBR322 DNA was investigated. The compounds produced qualitatively similar patterns of alkylation, with higher levels of alkylation at runs of guanines. The compounds were also tested for their ability to act as direct mutagens in Salmonella typhimurium TA98 and TA100. None of the compounds caused mutations in the TA98 frameshift mutagenesis assay. In the strain TA100, where mutation of a specific guanine by base-pair substitution produces reversion, all compounds were found to produce mutations, but the levels of mutagenicity did not correlate at all with the levels of DNA alkylation. The ratio of mutations to adducts varied at least 14-fold among the various N7-guanyl adducts examined.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of the DNA-alkylating properties and mutagenic responses of a series of S-(2-haloethyl)-substituted cysteine and glutathione derivatives. 226 77

Prostaglandin D synthetase activity in the cytosol (100,000 x g, 1-h supernatant) fraction of peritoneal mast cells of adult rats (105.0 nmol/min/mg protein) was the highest among such activities in various rat tissues and cells. As judged by the absolute requirement for glutathione for the reaction (Km = 300 microM), the Km value for prostaglandin H2 (200 microM), and insensitivity of the activity to 1 mM 1-chloro-2,4-dinitrobenzene, the enzyme in mast cells was similar to rat spleen prostaglandin D synthetase and differed from rat brain prostaglandin D synthetase or glutathione S-transferase, all of which catalyze the isomerase reaction from prostaglandin H2 to prostaglandin D2. In immunotitration analyses, the activity in mast cells showed a titration curve exactly identical with that of the purified spleen-type enzyme and almost completely absorbed by an excess amount of antibody against this enzyme, but it remained unchanged after incubation with antibodies against the brain-type enzyme and glutathione S-transferase isozymes thus far purified. In Western blot after two-dimensional electrophoresis of crude extracts of mast cells, a single immunoreactive spot was observed with antibody against the spleen-type enzyme at the same position as that of the purified enzyme (Mr = 26,000, pI = 5.2). Furthermore, the immunoreactive protein obtained from mast cells showed the same peptide fingerprints as those of the purified spleen-type enzyme, after partial digestion with Staphylococcus aureus V8 protease or trypsin. In immunoperoxidase staining, the immunoreactivity of the spleen-type enzyme was found in the cytosol of tissue mast cells in various organs such as thymus, intestine, stomach, and skin of adult rats. These findings indicate that prostaglandin D2 is produced by the spleen-type synthetase in mast cells of various tissues.
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PMID:Mast cells contain spleen-type prostaglandin D synthetase. 240 60

The cellular localization of glutathione-requiring PGD synthetase, which catalyzes the predominant formation of PGD2 in various peripheral tissues, was investigated in adult rats by immunoperoxidase-staining with a polyclonal antibody specific for this enzyme. Although the 25 N-terminal amino acid residues of synthetase are 56% identical and 76% similar to those of several rat glutathione S-transferase subunits, the antibody cross-reacted only with synthetase in dot blotting and was nearly completely inactive with all transferase isozymes thus far purified. In Western blotting after SDS-PAGE of crude extracts of rat spleen, the antibody showed a single positive band at the same position as that of the purified enzyme (Mr = 26,000). The positive immunocytochemical stain was found in a number of histiocytes and/or dendritic cells in spleen, thymus, and Peyer's patch of intestine. The immunostain was also observed in such cells in lamina propria of the villus in small intestine and colon, in submucosal layer of stomach, and in Kupffer cells in liver. Immunoelectron microscopy confirmed that immunoreactivity of this enzyme was distributed in cytoplasm of those cells. Such immunoreactive cells were not observed in brain, spinal cord, kidney, heart, testis, and skeletal muscle. These observations suggest that PGD2 is produced by glutathione-requiring PGD synthetase localized in these types of APC in various tissues and may play a critical role in dictating the progression of immune responses.
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PMID:The major source of endogenous prostaglandin D2 production is likely antigen-presenting cells. Localization of glutathione-requiring prostaglandin D synthetase in histiocytes, dendritic, and Kupffer cells in various rat tissues. 250 61

A 64-centiMorgan linkage map of mouse chromosome 9 was developed using cloned DNA markers and an interspecific backcross between Mus spretus and the C57BL/6J inbred strain. This map was compared to conventional genetic maps using six markers previously localized in laboratory mouse strains. These markers included thymus cell antigen-1, cytochrome P450-3, dilute, transferrin, cholecystokinin, and the G-protein alpha inhibitory subunit. No evidence was seen for segregation distortion, chromosome rearrangements, or altered genetic distances in the results from interspecific backcross mapping. Regional map locations were determined for four genes that were previously assigned to chromosome 9 using somatic cell hybrids. These genes were glutathione S-transferase Ya subunit (Gsta), the T3 gamma subunit, the low density lipoprotein receptor, and the Ets-1 oncogene. The map locations for these genes establish new regions of synteny between mouse chromosome 9 and human chromosomes 6, 11, and 19. In addition, the close linkage detected between the dilute and Gsta loci suggests that the Gsta locus may be part of the dilute/short ear complex, one of the most extensively studied genetic regions of the mouse.
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PMID:A molecular genetic linkage map of mouse chromosome 9 with regional localizations for the Gsta, T3g, Ets-1 and Ldlr loci. 257 8

The major DNA adduct formed from the carcinogen ethylene dibromide (1,2-dibromoethane, EDB) is S-[2-(N7-guanyl)ethyl]glutathione, resulting from the reaction of guanyl residues with the half-mustard S-(2-bromoethyl)glutathione, which is generated by glutathione S-transferase-catalyzed conjugation of EDB with glutathione. The half-life of the alkylating species [putative S-(2-bromoethyl)glutathione or the derived episulfonium ion] was estimated to be less than 10 s. However, the stability was enough for approximately half of the alkylating metabolites to leave isolated rat hepatocytes before reacting with nucleic acids. Treatment of isolated rat hepatocytes with diethylmaleate decreased covalent binding of EDB to DNA, but treatment with 1-phenylimidazole did not, consistent with the view that conjugative metabolism is of greater importance than oxidation with regard to DNA binding. When EDB was administered to rats in vivo, only one major adduct, S-[2-(N7-guanyl)ethyl]glutathione, was formed in liver or kidney. S-[2-(N7-Guanyl)ethyl]glutathione was found in liver and kidney DNA of rats treated with 1,2-dichloroethane, but other adducts were also present. The gamma-glutamyl transpeptidase inhibitor AT-125 [L-(alpha-(5S)-alpha-amino-S-chloro-4,5-dihydro-5-isoxazoleacetic acid] did not affect the level of EDB bound to DNA by glutathione-fortified rat kidney homogenates or bound to liver or kidney DNA in vivo. The in vitro half-life of S-[2-(N7-guanyl)ethyl]glutathione in calf thymus DNA was 150 h; the half-life of the adduct in rat liver, kidney, stomach, and lung was between 70 and 100 h. Isolated S-[2-(N7-guanyl)ethyl]glutathione did not react with DNA to form new adducts. These results provide a further basis for understanding the carcinogenic action of 1,2-dihaloethanes.
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PMID:Covalent binding of 1,2-dihaloalkanes to DNA and stability of the major DNA adduct, S-[2-(N7-guanyl)ethyl]glutathione. 287 Aug 1

When the amounts of primary prostaglandins formed from endogenous arachidonic acid were determined in homogenates of various tissues of adult rats, prostaglandin D2 was the major prostaglandin found in most tissues. It was formed actively in the spleen (3100 ng/g tissue/5 min at 25 degrees C), intestine (2600), bone marrow (2400), lung (1100), and stomach (630); moderately in the epididymis, skin, thymus, and brain (140-340); and weakly in other tissues (less than 100). Addition of exogenous arachidonic acid (1 mM) accelerated the formation of prostaglandin D2 in all tissues as follows: spleen (15,000); bone marrow, intestine, thymus, liver, and lung (1600-5200); stomach, adrenal gland, epididymis, brain, salivary gland, skin, spinal cord, and seminal vesicle (380-1000); and other tissues (80-310). The activity of prostaglandin D synthetase (prostaglandin-H2 D-isomerase) was detected in 100,000g supernatants of almost all tissues. As judged by glutathione requirement for the reaction, inhibition of the activity by 1-chloro-2,4-dinitrobenzene, and immunotitration or immunoabsorption analyses with specific antibodies, the enzyme in the epididymis, brain, and spinal cord (1.8-9.2 nmol/min/mg protein) was glutathione-independent prostaglandin D synthetase (Y. Urade, N. Fujimoto, and O. Hayaishi (1985) J. Biol. Chem. 260, 12410-12415). The enzyme in the spleen, thymus, bone marrow, intestine, skin, and stomach (2.0-57.1) was glutathione-requiring prostaglandin D synthetase (Y. Urade, N. Fujimoto, M. Ujihara, and O. Hayaishi (1987) J. Biol. Chem. 262, 3820-3825). The activity in the kidney and testis (3.7-4.5) was catalyzed by glutathione S-transferase. The activity in the liver, lung, adrenal gland, salivary gland, heart, pancreas, and muscle (0.6-5.1) was due to both the glutathione-requiring synthetase and the transferase.
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PMID:Prostaglandin D2 formation and characterization of its synthetases in various tissues of adult rats. 312 55

Dietary unsaturated fat is required for maximum induction of the hepatic mixed function oxidases (MFO) responsible for activating carcinogens to forms that may bind covalently to DNA. The aim of this study was to assess the influence of dietary fat type and content on the activities of some enzymes involved in activation and detoxification of the carcinogen benzo[a]pyrene (B[a]P). Modification of these changes by pretreatment with phenobarbital (PB) was also evaluated. Male rats were fed diet devoid of fat or containing 20% corn oil (CO) or 20% menhaden fish oil (MO) for 4 days. PB induced soluble glutathione S-transferase, a detoxifying enzyme, only in rats fed dietary fats. Microsomes from rats fed both types of dietary fat had increased levels of cytochrome P-450 (P-450) and PB induced P-450 only in rats fed these fats. Although ethoxycoumarin O-dealkylase was significantly elevated in the MO group, the induction by PB was not dependent on dietary fat type or level. Dietary fat increased microsome-catalyzed in vitro binding of [3H]-B[a]P to calf thymus DNA, especially in response to PB. Menhaden oil depressed B[a]P hydroxylation and PB treatment depressed this activity to the greatest extent in rats fed this diet. When calculated as B[a]P metabolized per unit of P-450, PB seems to induce a P-450 in fat fed animals having lower affinity and capacity for B[a]P hydroxylation and activation than in rats fed the fat-free diet.
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PMID:In vitro activation and resultant binding of benzo[a]pyrene to DNA by microsomes from rats fed corn and menhaden oils. 348 49


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