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 of GST as a vaccine candidate against liver fluke infection in ruminants was studied by vaccinating sheep (n = 9) with GST purified from adult worms of Fasciola hepatica and challenging with 500 F. hepatica metacercariae. The immunization induced a high antibody response to GST in contrast to the poor or undetectable response to this Ag observed in naturally infected sheep. Throughout the trial, the progress of the fluke infection was monitored by measuring RBC hemoglobin levels, the extent of liver damage and the fecal egg output in the sheep. This analysis indicated that a subpopulation (n = 4) of the GST vaccinated animals exhibited no anemia, reduced liver damage and a lower mean fecal egg count relative to the infected control group suggesting a lower fluke burden in these animals. Worm burdens in the livers of the GST vaccine group (107 +/- 22) were 57% lower than in the infected control group (250 +/- 25). The subpopulation of the GST vaccine group demonstrated a 78% reduction in mean worm burdens relative to the control group. These results show that GST of adult F. hepatica is a novel Ag that can significantly protect sheep against liver fluke infection. The results suggest that the immune response to GST is directed to the juvenile worm reducing the number of worms that can establish in the liver of the vaccinated animals.
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PMID:Glutathione S-transferase. Novel vaccine against Fasciola hepatica infection in sheep. 197 49

Enzyme catalyzed detoxication reactions are one of the primary defenses organisms have against chemical insult. This article reviews current chemical approaches to understanding the cooperative role of enzymes in the metabolism of foreign compounds. Emphasis is placed on chemical and stereochemical studies which help elucidate the mechanism of action and active-site topologies of the detoxication enzymes. The stereoselectivity of the cytochromes P-450 and flavin containing monooxygenases as well as the role of hemoglobin and lipid peroxidation in the primary metabolism of xenobiotics is discussed. Current knowledge of the mechanism and stereoselectivity of epoxide hydrolase is also presented. Three enzymes involved in secondary metabolism of xenobiotics, UDP-glucuronosyltransferase, sulfotransferase and glutathione S-transferase are discussed with particular emphasis on active site topology and cooperative participation with the enzymes of primary metabolism.
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PMID:Enzyme-catalyzed detoxication reactions: mechanisms and stereochemistry. 311 76

Phenylhydrazine when injected into the mouse acts in two phases. At an early stage it provokes directly in the erythrocytes as well as in the liver a decrease in the concentration of acid soluble nonprotein thiol groups. Indirectly it causes a later and more lasting increase in glutathione S-transferase and glucose-6-phosphate dehydrogenase activities in the erythrocytes, due mostly to a renewal of the population of these cells, and in glucose-6-phosphate dehydrogenase activity in the liver due to a decrease in hepatic glutathione. Thus, modifications in the erythrocytes are mainly due first to a strong oxidation of hemoglobin and afterwards to the renewal of the population. In the liver, modifications are mostly induced by consumption of reduced glutathione and secondary activation of the pentose cycle. It is suggested that there is a similarity between this chemical aggression and an inflammatory process.
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PMID:Influence of phenylhydrazine on the antioxidant system of the erythrocytes and the liver in mice. 671 4

The metabolism of [75Se]selenite was studied in rhesus monkeys. In blood samples taken various times after injection, Sephadex G-150 gel filtration revealed that the majority of the 75Se was associated with hemoglobin and low-molecular-weight compounds in erythrocytes up to 24 hours after selenium injection. Subsequently a gradual increase of 75Se occurred in glutathione peroxidase (GSH-Px) with a concurrent decrease of label with hemoglobin. In contrast to the erythrocytes, over 80% of the labeled selenium in plasma was associated with one peak 3 hours and later after injection. This major protein eluted at a position similar to GSH-Px on gel filtration, but subsequent chromatography on diethylaminoethyl (DEAE)-Sephacel separated the radiolabeled protein from GSH-Px. Gel filtration of heart, muscle, brain and pancreas cytosol revealed two major selenium-containing proteins, whereas one was predominant in liver and kidney. The major selenium peak was associated with GSH-Px in liver but not in the kidney. GSH-Px activity with either organic or inorganic peroxides as substrates and glutathione transferase activity were higher in liver than kidney.
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PMID:Metabolism of [75Se]selenite by rhesus monkeys. 674 31

Erythrocyte glutathione (GSH) can be rapidly depleted by incubating the cells with 1-chloro-2,4-dinitrobenzene (CDNB), which forms 2,4-dinitrophenyl-S-glutathione with GSH through the reaction catalyzed by glutathione S-transferase. GSH-CDNB conjugate thus formed stays undegraded within the erythrocytes. This indicates that in the erythrocytes, mercapturic acid pathway is inoperative. Depletion of GSH in the intact erythrocytes by CDNB results in rapid oxidation of large amounts of hemoglobin to methemoglobin. When glutathione S-transferase-free hemolysate of erythrocytes is incubated with CDNB, the depletion of GSH as well as methemoglobin formation are minimal. Glutathione peroxidase and glutathione reductase activities of the erythrocytes are not affected by CDNB. These studies provide a specific enzymatic method for rapid removal of erythrocyte GSH and also indicate that GSH is vital in maintaining a reduced environment within the erythrocytes.
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PMID:Enzymatic conjugation of erythrocyte glutathione with 1-chloro-2,4-dinitrobenzene: the fate of glutathione conjugate in erythrocytes and the effect of glutathione depletion on hemoglobin. 727 4

Vinyl carbamate epoxide (VCO) is believed to be the metabolite of ethyl carbamate (EC) ultimately responsible for its carcinogenic effects. This study investigates the role of glutathione (GSH) in protection against VCO-mediated adduct formation, and the involvement of glutathione S-transferases (GSTs) in detoxification of VCO. Formation of 1,N6-ethenoadenosine from VCO and adenosine in vitro was employed as a measure of VCO toxicity. GSH inhibited formation of ethenoadenosine in a concentration-dependent manner at concentrations ranging from 1 to 8 mM. This effect was significantly enhanced by addition of rat liver GST. Mouse liver cytosol was also found to inhibit formation of ethenoadenosine in a concentration-dependent manner, and the inhibition was relieved by addition of S-octylglutathione, a competitive inhibitor of GST. Pretreatment of mice with 1% dietary (2(3)-tert-butyl-4-hydroxyanisole (BHA) caused parallel increases in cytosolic GST activity and cytosolic enhancement of detoxification of VCO by GSH. Furthermore, BHA increased hepatic steady-state concentrations of GSH greater than twofold. The effect of BHA on detoxification of EC in vivo was examined using formation of 2-oxoethylvaline (OEV) adducts of hemoglobin as a biomarker. Pretreatment with BHA decreased overall formation of OEV adducts 23%. The major conclusions of this study are (1) VCO can be detoxified by spontaneous conjugation with GSH, (2) conjugation of VCO with GST can be catalyzed by GST(s), (3) pretreatment with BHA protects against binding of active EC metabolites in vitro and in vivo, and (4) the protective effect of BHA against EC is mediated by increases in GST activity and GSH concentration.
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PMID:Detoxification of vinyl carbamate epoxide by glutathione: evidence for participation of glutathione S-transferases in metabolism of ethyl carbamate. 748 30

In order to validate previous field observations by the authors on whitefish, Coregonus lavaretus L. s.l., a 30-day laboratory experiment with concentrations (0, 1.3, 2.3, 3.5, and 7 vol%) of bleached kraft pulp and paper mill effluent (BKME) simulating those occurring in a polluted lake was conducted. Chlorine dioxide had almost entirely replaced chlorine gas in the bleaching of pulp. As a consequence, the concentrations of adsorbable organic halogens and chlorinated phenolics (CPs) in BKME were significantly lowered compared to earlier studies. This reduction was also seen in the concentrations of CPs in the bile and CPs and extractable organic halogens in the intestinal lipids: the concentrations were low and did not depend on the dilution of BKME. In contrast, the resin acid content of bile decreased with decreasing BKME concentration. The growth of fish was speeded up in all BKME concentrations. However, at the highest BKME concentration (7 vol%) the increase was lowest. The induction of hepatic ethoxyresorufin O-deethylase (EROD) activity revealed strong dose-response relationship with BKME. At 3.5 vol% BKME (corresponding to a distance of 3.3 km from the mill sewer in the field) the EROD activity increased 12-fold. There was a tendency for lower activity of uridinediphosphate glucuronosyltransferase in the liver, but the decrease (34%; P < 0.05) was statistically significant only at 7 vol% BKME. The activity of liver glutathione S-transferase remained unchanged. All dilutions of BKME significantly depressed the concentrations of plasma immunoglobulin M (IgM). Erythrocytic concentrations of nucleotide triphosphates decreased and of sodium increased as the BKME concentration increased. Also some other blood parameters (hematocrit, hemoglobin, plasma glucose, and aspartate aminotransferase) were changed in all BKME exposures, although without obvious dependence on effluent concentration. In conclusion, there was a good agreement between field studies and laboratory experiments using BKME concentrations occurring in the field, confirming close or similar causes for responsive toxicity endpoints.
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PMID:Physiological toxicity of low-chlorine bleached pulp and paper mill effluent on whitefish (Coregonus lavaretus L. s.l.): a laboratory exposure simulating lake pollution. 749 61

The skin is the major environmental interface of the human body and is repeatedly exposed to a broad array of exogenous chemicals potentially capable of causing toxicity. In the present study we have applied 3, 6 or 12 ml leaded gasoline/kg body weight to the skin of adult male Swiss mice for 7 consecutive days and then sacrificed the animals on 8th day after an overnight fast. Glutathione (GSH) concentration, lipid peroxidation and other GSH-dependent enzyme activities were measured in skin, liver, brain and blood tissues of the mice. Topical application of 12 ml/kg gasoline caused a significant increase in water consumption by the animals, although, their body weight and food consumption was not significantly affected. A 40-60% decrease in blood concentration of glucose, triglyceride, and cholesterol was also observed after the treatment. The hemoglobin concentration, GSH content, lipid peroxidation and glucose 6-phosphate dehydrogenase activity of erythrocytes were not significantly affected by the gasoline treatment. However, a decrease in GSH concentration (16-21%), lipid peroxidation (30-60%) and glutathione S-transferase (GST) activity (30-40%) was observed in skin, liver and brain after gasoline application. Western blot analysis of tissues using antibodies against GST isoenzymes demonstrated an alteration in the expression of various GST isoenzymes after gasoline treatment. Our results suggest that topical exposure of gasoline causes some deleterious effects on skin and extracutaneous tissues.
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PMID:Alteration of glutathione, glutathione S-transferase and lipid peroxidation in mouse skin and extracutaneous tissues after topical application of gasoline. 778 Aug 31

The nm23-H1 gene is regarded as a human homologue of the mouse nm23 gene, which was expressed in a non-metastatic subline of mouse melanoma K-1735. The expression levels of nm23-H1 mRNA and the levels of protein during induced differentiation of human leukemia cell lines were analysed. mRNA levels of the megakaryoblastic leukemia line MEG-01, which were induced to differentiate into megakaryocyte by TPA, decreased rapidly from 2 days after the start of treatment and became almost undetectable at day 4. Similar down-regulation of nm23-H1 mRNA was also observed in the induced differentiation of the promyelocytic leukemia line HL-60 by TPA, or DMSO into monocyte-macrophage lineage or granulocytes, respectively. The amount of Nm23-H1 protein was analysed by Western immuno-blot analysis using mouse antiserum raised against a recombinant fusion protein with glutathione S-transferase. The amount of Nm23-H1 protein also decreased during the induced differentiation of these leukemia cell lines. On the other hand, in the differentiation of the erythroleukemia line K562 by hemin, levels of both mRNA and protein of Nm23-H1 elevated transiently, then reduced to the original level. When MEG-01 and K562 were stably transfected with nm23-H1 cDNA, MEG-01 transfectants showed reduced sensitivity to the induction of differentiation, whereas K562 transfectants were better induced to synthesize hemoglobin than controls. These findings suggest the possibility that Nm23-H1 protein plays an important role to maintain the proliferation of immature leukemic cells in MEG-01 and HL-60, but it may also play a role in the early stage of K562 differentiation, possibly in the different manner.
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PMID:Alteration of nm23 gene expression during the induced differentiation of human leukemia cell lines. 805 9

Genetic polymorphisms for six blood groups, three red cell enzymes, three serum proteins, and hemoglobin were examined in sixteen central Indian tribal populations. Nine of the tribes belonged to Orissa, five to Madhya Pradesh, and two to Maharashtra. Eleven tribes spoke the Dravidian language, three Indo-Ayran, and two the language of the Austro-Asiatic families. The population structure of these tribal populations was analyzed at the inter- and intrastate and linguistic levels, using data for 13 genetic systems (38 alleles or haplotypes). Nine of the 13 loci showed significant heterogeneity in the 16 tribes, and the pattern of heterogeneity was also discernible in the different states and in the Dravidian-speaking tribes. As expected, the extent of genetic differentiation or gene diversity was the highest so far reported from central India. The mean FIS and HS for each locus in the different state, linguistic, and total tribal groups were consistently higher than the FST and GST values, respectively, showing that the genetic structure of each tribe is highly influenced by inbreeding. In a genetic affinity analysis by genetic distance the Indo-Aryan and Austro-Asiatic language groups showed little affinity with each other, although there was some tendency toward geographic affinity. The present analysis indicates that, in addition to genetic drift, gene flow, and selection, the genetic structure of the populations of central India is also highly influenced by sociocultural adaptation and inbreeding.
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PMID:Population structure and genetic differentiation among 16 tribal populations of central India. 890 97


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