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)

An active biomonitoring experiment was performed using mussels collected at a clean site, Fier d'Ars, and transplanted to two locations, outside the harbor of La Rochelle and in the Baie de L'Aiguillon along the coast of Charentes (French Atlantic coast) beginning in April for several months. Mussels were collected in June and October. The cadmium, copper, and zinc concentrations of all resident and transplanted mussel samples and the polycyclic aromatic hydrocarbon and polychlorinated biphenyl concentrations in some mussel samples and in the sediment samples were determined. Mussel response was evaluated for several biochemical biomarkers: concentrations of metallothionein, activities of glutathione S-transferase and acetylcholinesterase (AChE) and levels of thiobarbituric reactive substance (TBARS). The physiological status of the animals was assessed using the condition index. A principal component analysis performed with the chemical and biochemical results of the evaluations of the resident and transplanted mussels collected in June allowed them to be separated into three groups: resident mussels from la Rochelle with high metal and TBARS levels, resident mussels from Baie de L'Aiguillon with a very high condition index, and resident mussels from Fier d'Ars and transplanted mussels at La Rochelle and Baie de L'Aiguillon with low TBARS and AChE activities. Strong seasonal variation from June to October of all parameters was noted. Mussels transplanted to La Rochelle appeared to be the most "polluted" in their pollutant concentrations and biochemical responses; moreover, the La Rochelle site had the highest concentration of organics in sediments of all the sites. The choice of Fier d'Ars as a reference site may be questionable because some of the biomarker responses of the mussels were higher than expected there, although these pollutants in mussels and sediment were present at the lowest concentrations measured.
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PMID:Multimarker approach in transplanted mussels for evaluating water quality in Charentes, France, coast areas exposed to different anthropogenic conditions. 1450 81

Sulforaphane (SUL) is one member of the isothiocyanate class of cancer chemopreventive compounds that has been shown to be effective in blocking initiation and progression of carcinogenesis. Previously, many studies have shown that SUL can potently induce phase II detoxifying enzymes, which contributes to its chemopreventive functions. In this study, we used 4967 oligonucleotides microarray to assess the genes that are modulated by SUL in in vivo rat livers, as well as time course of expression of these genes. The pharmacokinetics of SUL was assessed after oral dose of 50 micromol of SUL. The plasma concentration occurred at 1 h and peaked around 20 microM at 4 h after dosing and declined with a half-life of about 2.2 h. Analysis of the gene expression data found various clusters of genes that are important in cellular defense mechanisms and cell cycle regulation. The most robust cluster of genes is the metallothionein-like genes (MT-1/2 and MT-1a), which are increased up to 10-fold by 2 to 4 h after SUL dosing. The second cluster of genes is the glutathione S-transferase-A3-like genes, which include aflatoxin B1 aldehyde reductase and aldehyde oxidase. These genes are increased slightly by 4 h and peaked at 12 h. Real-time polymerase chain reaction was performed to authenticate the mRNA expression of some of these genes. In summary, this in vivo study of SUL provides the first clue as to the plasma concentrations of SUL, in vivo mitogen-activated protein kinase activations in rat livers, as well as what other genes are modulated in addition to phase II detoxifying genes. The results from this study may yield better insights for its chemopreventive functions.
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PMID:In vivo pharmacokinetics and regulation of gene expression profiles by isothiocyanate sulforaphane in the rat. 1498 20

Isoforms of metallothionein in the digestive gland of control and experimentally Cd-exposed mussels (Mytilus edulis) (200 microg L(-1) Cd2+ and 400 microg L(-1) Cd2+; 20 days) were studied using the reverse transcriptase-polymerase chain reaction. In addition, glutathione S-transferase (GSTpi) primers were designed to evaluate the reduction in the antioxidant defense systems (glutathione) accompanying the aging process in the same organisms. Following experimental exposure, an accumulation of Cd was observed in the digestive gland of exposed mussels, both adults and juveniles, up to 500 times higher than in the control. An induction of the dimeric form MT20 II was detected in 400 microg L(-1) exposed mussels, as well as a visible inhibition of the monomeric form MT10 IV. After 20 days of exposure juveniles expressed increased GSTpi compared with adults. Results reveal individual variation of both metallothioneins and GSTpi expression among control and Cd2+-exposed mussels of different ages. The ecotoxicological significance of MT utilization in biomonitoring of seawater for trace metals has been considered in light of these results.
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PMID:Cadmium induction of metallothionein isoforms in juvenile and adult mussel (Mytilus edulis). 1499 21

Inorganic arsenicals are clearly toxicants and carcinogens in humans. In mammals, including humans, inorganic arsenic often undergoes methylation, forming compounds such as monomethylarsonic acid (MMAs(V)) and dimethylarsinic acid (DMAs(V)). However, much less information is available on the in vitro toxic potential or mechanisms of these methylated arsenicals, especially MMAs(V). We studied the molecular mechanisms of in vitro cytolethality of MMAs(V) using a rat liver epithelial cell line (TRL 1215). MMAs(V) was not cytotoxic in TRL 1215 cells even at concentrations exceeding 10 mM, but it became weakly cytotoxic and induced both necrotic and apoptotic cell death when cellular reduced glutathione (GSH) was depleted with the glutathione synthase inhibitor, l-buthionine-[S,R]-sulfoximine (BSO), or the glutathione reductase inhibitor, carmustine. Similar results were observed in the other mammalian cells, such as human skin TIG-112 cells, chimpanzee skin CRT-1609 cells, and mouse metallothionein (MT) positive and MT negative embryonic cells. Ethacrynic acid (EA), an inhibitor of glutathione S-transferase (GST) that catalyses GSH-substrate conjugation, also enhanced the cytolethality of MMAs(V), but aminooxyacetic acid (AOAA), an inhibitor of beta-lyase that catalyses the final breakdown of GSH-substrate conjugates, had no effect. Both the cellular GSH levels and the cellular GST activity were increased by the exposure to MMAs(V) in TRL 1215 cells. On the other hand, the addition of exogenous extracellular GSH enhanced the cytolethality of MMAs(V), although cellular GSH levels actually prevented the cytolethality of combined MMAs(V) and exogenous GSH. These findings indicate that human arsenic metabolite MMAs(V) is not a highly toxic compound in mammalian cells, and the level of cellular GSH is critical to its eventual toxic effects.
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PMID:Cellular glutathione prevents cytolethality of monomethylarsonic acid. 1499 80

To profile gene expression patterns involved in the direct myocardial effect of cholesterol-enriched diet-induced hyperlipidemia, we monitored global gene expression changes by DNA microarray analysis of 3200 genes in rat hearts. Twenty-six genes exhibited significant up-regulation and 25 showed down-regulation in hearts of rats fed a 2% cholesterol-enriched diet for 8 weeks as compared to age-matched controls. The expression changes of 12 selected genes were also assessed by real-time quantitative polymerase chain reaction. Genes with altered expression in the heart due to hyperlipidemia included procollagen type III, cofilin/destrin, tensin, transcription repressor p66, synaptic vesicle protein 2B, Hsp86, chaperonin subunit 5epsilon, metallothionein, glutathione S-transferase, protein kinase C inhibitor, ATP synthase subunit c, creatine kinase, chloride intracellular channel 4, NADH oxidoreductase and dehydrogenase, fibronectin receptor beta chain, CD81 antigen, farnesyltransferase, calreticulin, disintegrin, p120 catenin, Smad7, etc. Although some of these genes have been suspected to be related to cardiovascular diseases, none of the genes has been previously shown to be involved in the mechanism of the cardiac effect of hyperlipidemia.
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PMID:Cholesterol diet-induced hyperlipidemia influences gene expression pattern of rat hearts: a DNA microarray study. 1504 8

Acute (4 days) and chronic (14 days) effects of copper were evaluated on the antioxidant defenses of Laeonereis acuta (Polychaeta) collected in unpolluted (UP) and polluted (P) sites. In the acute assay (125 and 250 micro g Cu/l) superoxide dismutase (SOD) and glutathione S-transferase (GST) activities did not change, whereas catalase (CAT) increased in worms from both the sites. Lipid peroxidation was higher in copper exposed worms from the P site. In the chronic assay (62.5 micro g Cu/l) polychaetes from the P site showed enhanced activities of SOD, GST and CAT and higher contents of metallothionein-like proteins and sulfhydrils compared to worms from UP. Differences in responses between polychaetes from UP and P sites suggest that organisms from the polluted site, P, are more susceptible to oxidative stress conditions.
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PMID:Oxidative stress responses in two populations of Laeonereis acuta (Polychaeta, Nereididae) after acute and chronic exposure to copper. 1504 43

Specimens of sea bass (Dicentrarchus labrax) were placed in cages for 1 month in spring and autumn at different locations in the Bay of Cannes (NW Mediterranean). Biochemical markers evaluated were: ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST) activities in fish livers and acetylcholinesterase (AChE) activity in fish muscle. EROD and GST activities were higher in front of the outlet for the wastewater plant of Cannes and in the harbour than outside the marina. High EROD and GST activities may be induced by petrol hydrocarbons and/or polychlorinated biphenyls (PCBs). AChE was low in the muscles of the fish caged in the harbour compared with samples from the other cages. Low AChE activity could suggest the presence of organophosphorus and carbamate compounds in seawater from the harbour. Mussels (Mytilus galloprovincialis) were caged off Cannes for the same periods as the fishes. Heavy metal, metallothionein (MT) concentrations and lysosomal membrane stability were evaluated in the digestive gland of the mussels. Results show low heavy metal and MT concentrations, implying low metal concentrations in the surrounding waters. High lysosomal membrane stability revealed a good physiological status of these animals after caging. The whole set of data indicates that seawater in the Bay of Cannes appeared to be unpolluted as regards pollutants which may induce the measured biomarkers, except in restricted areas.
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PMID:Evaluation of biomarkers in caged fishes and mussels to assess the quality of waters in a bay of the NW Mediterranean Sea. 1509 98

The purpose of this study was to investigate the adaptive mechanisms of hydrogen peroxide-supersensitive AML cells against the reactive oxygen species (ROS). Their scavenging capacity against ROS was determined using a fluorometric probe in the doxorubicin-resistant AML-2/DX100 cell characterized by the down-regulation of catalase. AML-2/DX100 cells had more scavenging capacity against endogenous pro-oxidants than did the parental cells AML-2/WT, suggesting that an anti-oxidant adaptation against ROS occurred. cDNA microarrays for 8000 human genes revealed that among 21 anti-oxidant genes, each four gene was up- and down-regulated more than 1.5-fold in AML-2/DX100 compared with AML-2/WT. The mRNA expression of glutathione S-transferase Pi, peroxiredoxin 2, thioredoxin 2, and glutaredoxin was elevated whereas that of peroxiredoxin 3, metallothionein-1F, superoxide dismutase 2, and thioredoxin reductase 1 was depressed. The result indicates that the down-regulation of certain anti-oxidant mechanisms can be compensated for by the up- and down-regulation of the other anti-oxidant mechanisms.
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PMID:Anti-oxidant adaptation in the AML cells supersensitive to hydrogen peroxide. 1515 39

Freshwater mussels, Elliptio complanata, were caged in special benthic pens and were immersed at one upstream (Ups) site and two downstream sites (8 and 11 km) of a primary-treated municipal effluent plume for 1 year. The levels of metallothionein-like proteins (MT), lipid peroxidation, protein-free DNA strands and glutathione S-transferase (GST) activity were assayed in digestive gland, gill and gonad tissues to evaluate biological effects and damage. The levels of monoamines (serotonin and dopamine) in nerve ganglia, ATP-dependent transport activity and monoamine oxidase (MAO) activity were also investigated in the homogenates, synaptosomes and mitochondria, respectively. Results showed that significant amounts of sediment accumulated in cages and 82% of mussels survived the yearlong exposure period at the downstream sites. MT-like proteins were induced in all tissues with the following response intensity: gill (3-fold), digestive gland (1.4-fold) and gonad tissues (1.3-fold). Lipid peroxidation decreased (2.5-fold) in digestive gland but increased in gill (1.6-fold) and in gonad tissues (1.5-fold). GST activity was readily increased in digestive gland (2.5-fold), suggesting the presence of organic contaminants in the plume. Levels of protein-free DNA strands did not vary significantly in digestive gland and gill tissues but were significantly reduced in gonad tissues (2.5-fold) relative to the upstream site. In visceral nerve ganglia, both serotonin and ATP-dependent serotonin transport decreased 1.7-fold with a 4-fold increase of 5-hydroxyindole acetate (5-HIAA, a serotonin metabolite) level relative to the upstream site. However, MAO activity was somewhat reduced at downstream sites (0.7- to 0.9-fold of the activity at the upstream site). Dopamine levels were found to be decreased (1.5-fold), but dopamine ATP-dependent transport activity was increased 1.8-fold, suggesting reduced dopaminergic activity. These results indicate that estrogenic chemicals are likely at play, and the increased dopamine and decreased serotonin ATP-dependent transport suggest that the municipal plume was serotonergic for mussels located at the downstream sites. Mussels exposed for 1 year display a complex but characteristic pattern of responses that could lead to harmful health effects including neuroendocrine disruption of reproduction.
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PMID:Endocrine disruption and health effects of caged mussels, Elliptio complanata, placed downstream from a primary-treated municipal effluent plume for 1 year. 1531 44

Osteopontin is a crucial factor for initiation of Th1 immune reaction. Previously, we established transgenic mice expressing osteopontin in hepatocytes, in which lymphocyte infiltration occurred spontaneously at 12 weeks of age and liver necrosis at 24 weeks of age. This liver necrosis may develop through provocation by excessive Th1 immune reaction, but it is also possible that hepatocytes become fragile under abundant osteopontin in the cytoplasm. Thus, gene expression profiles in the liver were evaluated to seek such contributing factors in the transgenic mice. On DNA microarray analysis of 3774 mouse genes, 16 genes were selected as hepatic genes significantly up-regulated in the transgenic mice aged 8 weeks than in the negative littermate, which included mRNAs of cytoprotective metallothionein and glutathione S-transferase (GST). Hepatic up-regulations of both genes were also seen by Western blotting. Liver necrosis in the centrilobular areas developed after carbon tetrachloride treatment, but its histological extent and plasma ALT activities were significantly smaller in the transgenic mice aged 8 weeks than in the wild-type C57BL/6 control mice. We conclude that cytoprotective function of the liver is increased through up-regulated expressions of metallothionein and GST, and thereby susceptibility of hepatocytes to the stress may be less possible, if any, in the development of spontaneous liver necrosis in transgenic mice expressing osteopontin in hepatocytes.
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PMID:Increased cytoprotective function in the liver of transgenic mice expressing osteopontin in hepatocytes. 1590 65


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