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 cytosolic glutathione S-transferases (GSTs) comprise a pivotal enzyme system protecting the cell from electrophilic compounds. It plays a major role in the detoxication of the primary and dihydrodiol epoxides of polycyclic aromatic hydrocarbons (PAHs), so that modulation of this enzyme system by PAHs will impact on their carcinogenic activity. The potential of six structurally diverse PAHs, namely benzo[a]pyrene (B[a]P), fluoranthene, benzo[b]fluoranthene (B[b]F), dibenzo[a,l]pyrene, dibenzo[a,h]anthracene (D[a,h]A) and 1-methhylphenanthrene, to modulate hepatic GST activity was investigated in human precision-cut slices and compared to rat slices, a species frequently used in long-term carcinogenicity studies; changes were monitored at the activity, using three different substrates, protein and mRNA levels. When activity was monitored using the alpha-class selective 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, B[b]F was the only PAH that caused an increase in activity, which was accompanied by a rise in the Ya immunoreacting band. In rat slices, in addition to B[b]F, B[a]P and D[a,h]A also enhanced activity, being paralleled with increased levels of the Ya immunoreacting band. In the rat, all PAHs elevated mRNA levels. In both human and rat liver slices, only B[b]F enhanced activity when 1-chloro-2,4-dinitrobenzene (CDNB) served as substrate. To investigate tissue differences, similar studies were undertaken in precision-cut rat lung slices, incubated with PAHs under identical conditions, using CDNB, as this was the only substrate for which activity could be detected; none of the PAHs studied stimulated activity. It is concluded that some PAHs have the potential to induce GST activity in human liver tissue and that species and tissue differences exist in the induction of this enzyme system in the rat. However, the extent of induction of GST activity is very modest compared with the effect these compounds have on CYP1 expression, the family responsible for their bioactivation, and it is unlikely to compensate for the enhanced production of reactive intermediates.
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PMID:Up-regulation of the glutathione S-transferase system in human liver by polycyclic aromatic hydrocarbons; comparison with rat liver and lung. 1838 59

The effect of exposure of Aedes aegypti larvae to sub-lethal doses of the pyrethroid insecticide permethrin, the organophosphate temephos, the herbicide atrazine, the polycyclic aromatic hydrocarbon fluoranthene and the heavy metal copper on their subsequent tolerance to insecticides, detoxification enzyme activities and expression of detoxification genes was investigated. Bioassays revealed a moderate increase in larval tolerance to permethrin following exposure to fluoranthene and copper while larval tolerance to temephos increased moderately after exposure to atrazine, copper and permethrin. Cytochrome P450 monooxygenases activities were induced in larvae exposed to permethrin, fluoranthene and copper while glutathione S-transferase activities were induced after exposure to fluoranthene and repressed after exposure to copper. Microarray screening of the expression patterns of all detoxification genes following exposure to each xenobiotic with the Aedes Detox Chip identified multiple genes induced by xenobiotics and insecticides. Further expression studies using real-time quantitative PCR confirmed the induction of multiple CYP genes and one carboxylesterase gene by insecticides and xenobiotics. Overall, this study reveals the potential of xenobiotics found in polluted mosquito breeding sites to affect their tolerance to insecticides, possibly through the cross-induction of particular detoxification genes. Molecular mechanisms involved and impact on mosquito control strategies are discussed.
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PMID:Cross-induction of detoxification genes by environmental xenobiotics and insecticides in the mosquito Aedes aegypti: impact on larval tolerance to chemical insecticides. 1840 32

Freshwater fish Carassius auratus were chosen as experimental animals, the hepatic biochemical responses to medium-term exposure of five PAHs were measured as ethoxyresorufin O-deethylase (EROD) activity (phase I) and glutathione S-transferase (GST) activity (phase II) to assess sub-lethal effects. The fold increases of EROD and GST activity were calculated and both increased in the order Fluoranthene < Fluorene < Benzo(b)fluoranthene < Benzo(g,h,i)perylene < Indeno(1,2,3-cd)-pyrene. The clear dose-response relationships were found for liver EROD and GST activity induced by PAHs. The enzyme EROD and GST in Carassius auratus were confirmed as useful biomarkers of exposure to both PAH and PAH-like compounds.
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PMID:The dose-response relationships for EROD and GST induced by polyaromatic hydrocarbons in Carassius auratus. 1903 69

Despite ubiquity of polycyclic aromatic hydrocarbons (PAHs) in the tropical environments, little information is available concerning responses of tropical fish to PAHs and associated toxicity. In the present study, effects of five PAHs containing two to four aromatic rings on hepatic CYP1A dependent ethoxyresorufin O-deethylase (EROD), glutathione S-transferase (GST) and serum sorbitol dehydrogenase (SDH) activities in Nile tilapia, a potential fish species for biomonitoring pollution in tropical waters, were evaluated. Results showed that EROD activities were induced by the PAHs containing four aromatic rings (pyrene and chrysene) in a dose dependent manner. However PAHs with two to three aromatic rings (naphthalene, phenanthrene and fluoranthene) caused no effect or inhibition of EROD activities depending on the dose and the duration. Fluoranthene was the most potent inhibitor. SDH results demonstrated that high doses of fluoranthene induced hepatic damage. GST activity was induced by the lowest dose of phenanthrene, fluoranthene and chrysene but high doses had no effect. The results indicate that induction of EROD enzyme in Nile tilapia is a useful biomarker of exposure to PAHs such as pyrene and chrysene. However EROD inhibiting PAHs such as fluoranthene in the natural environment may modulate the EROD inducing potential of other PAHs thereby influencing PAH exposure assessments.
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PMID:Modulation of ethoxyresorufin O-deethylase and glutathione S-transferase activities in Nile tilapia (Oreochromis niloticus) by polycyclic aromatic hydrocarbons containing two to four rings: implications in biomonitoring aquatic pollution. 2022 26

Relations between several stress oxidative biomarkers and aromatic polycyclic hydrocarbon (PAH) concentrations have been studied in wild sole, Solea senegalensis collected in the vicinity of a petrochemical industry. Antioxidant enzyme activities in eco-toxicological studies constitute excellent markers for exposure to a large variety of pollutants. The 16 PAHs in sediment as well as oxidative damage (LPO), activity of catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and PAHs type metabolites in sole liver were analysed. Significant correlations (p<0.05) were established between some biomarkers as GST, GPx and CAT and PAHs metabolites in liver (naphthalene, pyrene and phenanthrene) and PAHs concentrations in sediments (fluoranthene, acenaphthene, anthracene and chrysene). PAHs accumulated in the sediment and organisms are inducers of antioxidant defences. GST, GPx and CAT were robust biomarkers showing correlations with both PAHs in sediments and liver PAH metabolites showing different responses to low and high molecular weight PAHs.
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PMID:Biochemical effects and polycyclic aromatic hydrocarbons (PAHs) in senegal sole (Solea senegalensis) from a Huelva estuary (SW Spain). 2084 49

Glutathione transferases (GSTs) are phase II enzymes that detoxify a wide range of toxicants and reactive intermediates. One such class of toxicants is the ubiquitous polycyclic aromatic hydrocarbons (PAHs). Certain PAHs are known to cause developmental cardiac toxicity in fish. Herein, we explored the role of GST pi class 2 (GSTp2) in PAH- and PCB-induced cardiac toxicity in zebrafish (Danio rerio) embryos. We measured expression of GSTp2 in embryos exposed to individual and co-exposures of the PAHs benzo[k]fluoranthene (BkF), benzo[a]pyrene (BaP), and fluoranthene (FL) as well as 3,3',4,4',5-pentachlorobiphenyl (PCB-126). GSTp2 mRNA expression was induced by exposure to BkF, BaP, PCB-126, and BaP+FL and BkF+FL co-exposure. A splice junction morpholino was then used to knockdown GSTp2 in developing zebrafish. GSTp2 knockdown exacerbated the toxicity caused by co-exposures to BkF+FL and BaP+FL. However, GSTp2 knockdown did not affect PCB-126 toxicity. These results further suggest that pi class GSTs serve a protective function against the synergistic toxicity caused by PAHs in developing zebrafish.
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PMID:Glutathione transferase pi class 2 (GSTp2) protects against the cardiac deformities caused by exposure to PAHs but not PCB-126 in zebrafish embryos. 2226 88

The phytoplankton is the basis of food webs and also, may bioconcentrate different toxic substances. This phenomenon is well documented, but there are few studies on the toxic effects on the phytoplankton community. In the current study the relation of oxidative stress (TBARS, ROOH, RC=O) and antioxidant defenses (activities of SOD, CAT, GPx and GST) of two phytoplankton communities with BCF of heavy metals (Cu, Fe, Mn, Pb, Zn) and of PAHs (naphthalene, pyrene, indenol, benzo[a]pyrene, benzo[a]anthracene, benzo[b]fluoranthene) was tested. Three sampling surveys were conducted bimonthly on the surface and bottom at different sampling points in the lakes Menor and Mayor of the 2nd section of Chapultepec Park. Also negative and positive controls obtained in the laboratory were included. Toxicity relationships were analyzed using the integrated biomarker response (IBR). Both green algae and cyanobacteria dominated. The contents of ROOH and protein oxidation assessed as RC=O were higher in the Lago Menor, a water body that contains ancient sediments. Through the IBR it was demonstrated that these damages were influenced by Pb, indenol and benzo[b]fluoranthene. In contrast, TBARS content was higher in Lago Mayor, which has sediment in formation. Through IBR it was estimated that Cu, Fe, Mn, Pb, indenol and benzo[b]fluoranthene were related to this damage. However, oxidative stress was accompanied by an induction of CAT and SOD, in contrast, GPx and GST had low or null activity. The field data were similar to the positive controls. We demonstrated for the first time that, although the phytoplankton suffers oxidative stress elicited by metals and PAHs, this community is able to counter this damage through antioxidant defenses. The effects of organic or inorganic toxics in phytoplankton depend on their bioavailability that is modulated by the sediment and also by its physicochemical properties and the characteristics of the abiotic medium.
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PMID:Relations of oxidative stress in freshwater phytoplankton with heavy metals and polycyclic aromatic hydrocarbons. 2341 86

Polycyclic aromatic hydrocarbons (PAHs) are priority environmental mutagens and carcinogens that occur in the aquatic environment as mixtures rather than the individual compounds for which guidelines are issued. The present work aimed at understanding the interaction effects between carcinogenic and non-carcinogenic PAHs in a model marine fish (Dicentrarchus labrax) in realistic scenarios. Laboratory assays under ecologically-relevant parameters were conducted for 28 days with sediments spiked with low-moderate concentrations (250-800ngg(-1)) of two model PAHs, phenanthrene (non-carcinogenic) and benzo[b]fluoranthene (carcinogenic to experimental animals). Both PAHs induced hepatic histopathological changes that indicate metabolic failure and inflammation, especially in animals exposed to mixtures. Phenanthrene elicited biochemical changes better related to oxidative stress (lipid peroxidation, glutathione and glutathione S-transferase activity) and CYP function, whereas B[b]F disrupted metabolic responses and defences to toxicological challenge. Conversely, mixed PAHs yielded lesions and responses that, altogether, are compatible with the AHR dependent pathway (the basis of PAH mutagenicity), potentially generating supra-additive effects. Nonetheless, the low, ecologically-relevant, concentrations of PAHs diluted dose and time-response relations. Overall, although seemingly predicting the risk of individual PAHs, environmental guidelines may not apply to mixtures by underestimating adverse effects, which calls for a redefinition of standards when determining the true risk of toxicants under realistic circumstances.
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PMID:Effects of carcinogenic versus non-carcinogenic AHR-active PAHs and their mixtures: lessons from ecological relevance. 2570 30

Polycyclic aromatic hydrocarbon (PAH) compounds are persistent, carcinogenic, and mutagenic. When PAHs enter agricultural soils through sewage sludge, they pose an environmental risk to soil organisms, including earthworms. Therefore, we aimed to determine the toxic effects of PAHs on earthworms. Five PAHs were used: fluorene, anthracene, phenanthrene, fluoranthene, and pyrene. Only fluorene and phenanthrene exhibited toxicity (LC50 values 394.09 and 114.02 g L(-1), respectively) against the earthworm Eisenia fetida. None of the other PAHs tested in this study enhanced the mortality of adult earthworm until the concentrations reached to 1000 g L(-1). After exposure to PAHs, acetylcholinesterase (AChE) activity in E. fetida decreased in a concentration-dependent manner, and phenanthrene exhibited the strongest inhibitory effect on AChE, followed by fluorene. Activity of a representative detoxifying enzyme, carboxylesterase, was dramatically reduced in E. fetida exposed to all tested PAHs in comparison with that observed in the control test. The remaining glutathione S-transferase activity significantly decreased in E. fetida after exposure to PAHs. To profile small proteins <20 kDa, SELDI-TOF MS with Q10 ProteinChips was used, and 54 proteins were identified as being significantly different from the control (p = 0.05). Among them, the expressions of three proteins at 4501.8, 4712.4, and 4747.9 m/z were only enhanced in E. fetida exposed to anthracene and pyrene. One protein with 16,174 m/z was selectively expressed in E. fetida exposed to fluorene, phenanthrene, and fluoranthene. These proteins may be potential biomarkers for the five PAHs tested in E. fetida.
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PMID:Determination of biomarkers for polycyclic aromatic hydrocarbons (PAHs) toxicity to earthworm (Eisenia fetida). 2592 May 60

Biomarkers have been extensively used in monitoring programs with the aim of assessing the biological effects of pollutants on marine organisms and determining environmental status. Data obtained from these programs are sometimes difficult to interpret due to the large amount of natural variables affecting biological processes, which could act as confounding factors on biomarker responses. The main aim of this work was to identify the effect of one of these variables, the food availability, and consequently, the mussel nutritive status, on biomarker responses. For that purpose, mussels (Mytilus galloprovincialis) were conditioned to three different food rations for 2 months in order to create three mussel nutritive statuses and afterwards, each status was exposed to three nominal concentrations of fluoranthene (FLU) for 3 weeks. A battery of biomarkers was considered in this study to cover a wide range of organism responses, both physiological (scope for growth - SFG) and biochemical (superoxide dismutase - SOD, catalase - CAT, glutathione reductase - GR, glutathione peroxidase - GPx, glutathione-S-transferase - GST and phenoloxidase - PO activities, and lipid membrane peroxidation - LPO). The results obtained, evidenced that most of the studied biomarkers (SFG, SOD, CAT, GPx, and PO) were strongly affected by mussel nutritive status, showing higher values at lower status, whereas the effect of toxicant was not always evident, masked by the nutritive status effect. This paper demonstrates that toxicants are not the only source of variability modulating pollution biomarkers, and confirms nutritive status as a major factor altering biochemical and physiological biomarkers.
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PMID:Effect of nutritive status on Mytilus galloprovincialis pollution biomarkers: Implications for large-scale monitoring programs. 2627 8


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