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Glutathione Transferase (glutathione + transferase)
Selected AbstractsInsect glutathione transferases and insecticide resistanceINSECT MOLECULAR BIOLOGY, Issue 1 2005A. A. Enayati Abstract Glutathione transferases (GSTs) are a diverse family of enzymes found ubiquitously in aerobic organisms. They play a central role in the detoxification of both endogenous and xenobiotic compounds and are also involved in intracellular transport, biosynthesis of hormones and protection against oxidative stress. Interest in insect GSTs has primarily focused on their role in insecticide resistance. GSTs can metabolize insecticides by facilitating their reductive dehydrochlorination or by conjugation reactions with reduced glutathione, to produce water-soluble metabolites that are more readily excreted. In addition, they contribute to the removal of toxic oxygen free radical species produced through the action of pesticides. Annotation of the Anopheles gambiae and Drosophila melanogaster genomes has revealed the full extent of this enzyme family in insects. This mini review describes the insect GST enzyme family, focusing specifically on their role in conferring insecticide resistance. [source] Evaluation of the radioprotective effect of Liv 52 in miceENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 7 2006Ganesh C. Jagetia Abstract Liv 52 is a mixture of botanicals that is used clinically to treat various hepatic disorders. In this study, the radioprotective activity of Liv 52 was evaluated in mice given whole-body exposure to different doses of ,-radiation. In addition, a series of studies was conducted to explore the mechanism of radioprotection. Radioprotection was evaluated by the ability of Liv 52 to reduce both the frequency of bone marrow micronucleated erythrocytes and the lethality produced by 60Co ,-radiation. Mice were treated by oral gavage once daily for seven consecutive days with 500 mg/kg body weight Liv 52 or carboxymethylcellulose vehicle prior to radiation. Micronucleated polychromatic erythrocytes (MPCEs), micronucleated normochromatic erythrocytes (MNCEs), and the PCE/NCE ratio were measured at 0.25,14 days after exposure to whole-body radiation doses of 0, 0.5, 1.5, 3.0, or 4.5 Gy; animal survival was monitored after doses of 7, 8, 9, 10, 11, or 12 Gy. Pretreatment of mice with Liv 52 significantly reduced the frequency of radiation-induced MPCEs and MNCEs. Irradiation reduced the PCE/NCE ratio in a dose-related manner for up to 7 days following irradiation; Liv 52 pretreatment significantly mitigated against these reductions. Liv 52 treatment also reduced the symptoms of radiation sickness and increased mouse survival 10 and 30 days after irradiation. Liv 52 pretreatment elevated the levels of reduced glutathione (GSH), increased the activities of glutathione transferase, GSH peroxidase, GSH reductase, superoxide dismutase, and catalase, and lowered lipid peroxidation (LPx) and the activities of alanine amino transferase and aspartate aminotransferase 30 min after exposure to 7 Gy of ,-radiation. Liv 52 pretreatment also reduced radiation-induced LPx and increased GSH concentration 31 days following the exposure. The results of this study indicate that pretreatment with Liv 52 reduces the genotoxic and lethal effects of ,-irradiation in mice and suggest that this radioprotection may be afforded by reducing the toxic effects of the oxidative products of irradiation. Environ Mol. Mutagen., 2006. © 2006 Wiley-Liss, Inc. [source] Hepatic chemoprotective enzyme responses to 2-substituted selenazolidine-4(R)-carboxylic acidsJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 6 2006Wael M. El-Sayed Abstract In epidemiology and human supplementation studies, as well as many animal models, selenium has shown antitumorigenic activity. The mechanism of action, however, has not been satisfactorily resolved. Selenium supplementation affects many enzymes in addition to those where selenocysteine is an essential component. Such enzymes include cytoprotective detoxifying enzymes, and the regulation of these enzymes by a set of 2-substituted selenazolidine-4(R)-carboxylic acids (SCAs) has been investigated. Following seven consecutive daily doses of these prodrugs of L -selenocysteine, changes in hepatic enzyme activities and/or mRNA levels of glutathione transferase (GST), microsomal epoxide hydrolase (mEH), NAD(P)H-quinone oxidoreductase (NQO), UDP-glucuronosyltransferase (UGT), glutathione peroxidase (GPx), and thioredoxin reductase (TR) have been observed. Among the enzymes examined, UGTs and GPx were found to be the least affected. Among the compounds, 2-oxoSCA produced the most changes and 2-phenylSCA produced the least, none. For no two compounds was the pattern of changes identical, and for a single compound, few changes were reproduced in common by the two routes of administration investigated. In general, more changes were elicited following intraperitoneal (i.p.) administration than with the intragastric (i.g.) route. This dominance was typified by 2-butylSCA and 2-cyclohexylSCA where enzyme activity elevations (TR and mEH with both, NQO with 2-butylSCA) were seen only with the i.p. route. With 2-oxoSCA, however, GST, TR, and NQO activities were found to be elevated independent of route. Only with GST (both routes) and TR (i.p. route), elevations in mRNAs accompanied the 2-oxoSCA elicited elevations of activities at the time of sacrifice. For some enzymes, most notably mEH with compounds administered i.p., elevations in mRNAs were not manifest as increased enzyme activity. Thus, although constituting a closely related series of compounds, each 2-substituted SCA produced its own unique pattern of changes, and for most members, changes were predominant following i.p. administration. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:292,301, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20148 [source] Ethanol-induced alterations of the antioxidant defense system in rat kidneyJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 6 2006Diana Dinu Abstract We report here the effects of chronic ethanol consumption on the antioxidant defense system in rat kidney. Thirty-two male Wistar rats were randomly divided in two identical groups and were treated as follows: control group (water for fluid) and the ethanol-fed group (2 g/kg body weight/24 h). The animals were sacrificed after 10 weeks, and respectively 30 weeks of ethanol consumption, and the renal tissue was isolated and analyzed. Results revealed that kidney alcohol dehydrogenase activities increased significantly after ethanol administration, but the electrophoretic pattern of alcohol dehydrogenase isoforms was unmodified. The SDS polyacrylamidegel electrophoretic study of kidney proteins has revealed the appearance of two new protein bands after long-term ethanol consumption. The kidney reduced glutathione/oxidized glutathione ratio decreased, indicating an oxidative stress response due to ethanol ingestion. The malondialdehyde contents and xanthine oxidase activities were unchanged. The antioxidant enzymatic defense system showed a different response during the two periods of ethanol administration. After 10 weeks, catalase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase were activated, while superoxide dismutase, glutathione transferase, and ,-glutamyltranspeptidase levels were stationary. After 30 weeks, superoxide dismutase and glutathione peroxidase activities were unmodified, but catalase, glutathione transferase, ,-glutamyltranspeptidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities were significantly increased. Remarkable changes have been registered after 30 weeks of ethanol administration for glutathione reductase and glucose-6-phosphate dehydrogenase activities, including an increase by 106 and 216' of control values, respectively. These results showed specific changes in rat kidney antioxidant system and glutathione status as a consequence of long-term ethanol administration. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:386-395, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20101 [source] Quantification of urinary N -acetyl- S - (propionamide)cysteine using an on-line clean-up system coupled with liquid chromatography/tandem mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 4 2005Chien-Ming Li Abstract Acrylamide has been reported to be present in high-temperature processed foods and normal processed food intake could lead to significant acrylamide exposure. Acrylamide in vivo can be conjugated with glutathione in the presence of glutathione transferase. This conjugation product is further metabolized and excreted as N -acetyl- S -(propionamide)cysteine (NASPC) in the urine. NASPC could be considered a biomarker for acrylamide exposure. The objective of this study was to develop a highly specific, rapid and sensitive method to quantify urinary NASPC, serving as a biomarker for acrylamide exposure assessment. Isotope-labeled [13C3]NASPC was successfully synthesized and used as an internal standard. This urine mixture was directly analyzed using a newly developed liquid chromatographic/tandem mass spectrometric method coupled with an on-line clean-up system. The detection limit for this method was estimated as <5 µg l,1(0.4 pmol) on-column. The method was applied to measure the urinary level of NASPC in 70 apparently health subjects. The results showed that the NASPC urinary level was highly associated with smoking. Smokers had a significantly higher urinary NASPC level (135 ± 88 µg g,1 creatinine) than non-smokers (76 ± 30 µg g,1 creatinine). A highly sensitive and selective LC/MS/MS isotope dilution method was successfully established. With an on-line clean-up system, this system is capable of routine high-throughput analysis and accurate quantitation of NASPC in urine. This could be a useful tool for health surveillance for acrylamide exposure in a population for future study. Copyright © 2005 John Wiley & Sons, Ltd. [source] Thymoquinone supplementation induces quinone reductase and glutathione transferase in mice liver: possible role in protection against chemical carcinogenesis and toxicityPHYTOTHERAPY RESEARCH, Issue 9 2009Mahmoud N. Nagi Abstract Thymoquinone (TQ), the main constituents of the volatile oil from Nigella sativa seeds is reported to protect laboratory animals against chemical carcinogenesis and toxicity through mechanism(s) that is not fully understood. Among possible mechanism(s), protection could be mediated via induction of detoxifying enzymes, including quinone reductase and glutathione transferase. This study was undertaken to investigate whether oral administration of TQ increases the activities of quinone reductase and glutathione transferase in mice liver. Overdose of TQ, when administered intraperitoneally, caused a marked depletion of hepatic glutathione in both a time- and dose- dependent manner, a characteristic of a group of compounds known as Michael reaction acceptors which are known to act as inducers of enzymes that protect against chemical carcinogenesis and toxicity. TQ was given (1, 2 and 4 mg/kg/day p.o.) for five days to test the chemical inducibility of quinone reductase and glutathione transferase in mice liver. TQ administration produced significant increase in the activities of quinone reductase (147, 196 and 197% of control, respectively) and glutathione transferase (125, 152 and 154% of control, respectively). In conclusion, oral administration of TQ is effective in increasing the activities of quinone reductase and glutathione transferase and makes TQ a promising prophylactic agent against chemical carcinogenesis and toxicity. Copyright © 2009 John Wiley & Sons, Ltd. [source] Proteomic analysis of differentially expressed proteins in Penaeus vannamei hemocytes upon Taura syndrome virus infectionPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 19 2007Phattara-orn Chongsatja Abstract To understand molecular responses of crustacean hemocytes to virus infection, we applied 2-DE proteomics approach to investigate altered proteins in hemocytes of Penaeus vannamei during Taura syndrome virus (TSV) infection. At 24,h postinfection, quantitative intensity analysis and nano-LC-ESI-MS/MS revealed 11 forms of 8 proteins that were significantly up-regulated, whereas 9 forms of 5 proteins were significantly down-regulated in the infected shrimps. These altered proteins play important roles in host defense (hemocyanin, catalase, carboxylesterase, transglutaminase, and glutathione transferase), signal transduction (14-3-3 zeta), carbohydrate metabolism (acetylglucosamine pyrophosphorylase), cellular structure and integrity (beta-tubulin, beta-actin, tropomyosin, and myosin), and ER-stress response (protein disulfide isomerase). Semiquantitative RT-PCR and Western blot analysis confirmed the upregulation of 14-3-3 at both mRNA and protein levels. Interestingly, several altered protein spots were identified as fragments of hemocyanin. Mass spectrometric analysis showed that the hemocyanin spots at acidic and basic regions represented the C- and N-terminal hemocyanin fragments, respectively. As three-quarters of C-terminal fragments were up-regulated, whereas two-thirds of N-terminal hemocyanin fragments were down-regulated, we therefore hypothesize that C- and N-terminal hemocyanin fragments may have differential roles in hemocytes. Further investigation of these data may lead to better understanding of the molecular responses of crustacean hemocytes to TSV infection. [source] Effect of supplemental l -ascorbyl-2-polyphosphate in enriched live food on the antioxidant defense system of Penaeus vannamei of different sizes exposed to ammonia-NAQUACULTURE NUTRITION, Issue 5 2006W.-N. WANG Abstract The effects of supplemental l -ascorbyl-2-polyphosphate (APP) in enriched live food (Artemia) on reactive oxygen intermediate (ROI) and free radical scavenging enzyme (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione transferase) activities in the muscle of Penaeus vannamei of two sizes exposed to ambient ammonia-N, were investigated. Significantly, decreased ROI value was found in prawns fed on enriched Artemia compared with those fed on starved Artemia (P < 0.05); the decrease was 24% and 36%, respectively. In both size classes, the antioxidant enzyme activities in prawns fed on enriched Artemia were higher than in those fed on starved Artemia (P < 0.05). The results demonstrated that the supplementation of ascorbic acid in enriched live food (Artemia) enhanced the antioxidant capacity of prawn, increasing its defense system that may fight against environmental stress, leading to impaired ammonia toxicity. [source] Crystallization and preliminary X-ray crystallographic analysis of a highly stable mutant V107A of glutathione transferase from Anopheles dirus in complex with glutathioneACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 3 2006Jantana Wongsantichon An engineered mutant V107A of the dimeric glutathione transferase enzyme from Anopheles dirus (adgstD4-4) was cocrystallized with glutathione substrate using the hanging-drop vapour-diffusion method. The crystal diffracted to 2.47,Å resolution in space group P3221 (unit-cell parameters a = b = 49.4, c = 272.4,Å). Although the crystal morphology differed from that previously obtained for the wild-type enzyme, the crystal packing was the same. At 318,K, the engineered mutant showed an enzyme stability that was increased by about 32-fold, while possessing a similar catalytic function to the wild type. Structural determination will provide valuable understanding of the role of Val107. This residue is in the dimeric interface and appears to contribute towards enhancing the physical properties of the entire protein. [source] Insect glutathione transferases and insecticide resistanceINSECT MOLECULAR BIOLOGY, Issue 1 2005A. A. Enayati Abstract Glutathione transferases (GSTs) are a diverse family of enzymes found ubiquitously in aerobic organisms. They play a central role in the detoxification of both endogenous and xenobiotic compounds and are also involved in intracellular transport, biosynthesis of hormones and protection against oxidative stress. Interest in insect GSTs has primarily focused on their role in insecticide resistance. GSTs can metabolize insecticides by facilitating their reductive dehydrochlorination or by conjugation reactions with reduced glutathione, to produce water-soluble metabolites that are more readily excreted. In addition, they contribute to the removal of toxic oxygen free radical species produced through the action of pesticides. Annotation of the Anopheles gambiae and Drosophila melanogaster genomes has revealed the full extent of this enzyme family in insects. This mini review describes the insect GST enzyme family, focusing specifically on their role in conferring insecticide resistance. [source] Co-induction of glutathione- S -transferases and multidrug resistance associated protein by xenobiotics in wheat,PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 2 2003Frederica L Theodoulou Abstract Herbicide safeners are known to protect monocotyledonous crops from herbicide injury by accelerating the metabolism of herbicides. We have investigated the effects of the safener cloquintocet-mexyl, which protects small-grain cereals against the graminicidal herbicide, clodinafop-propargyl. Subtractive suppression hybridisation was used to identify wheat genes which are up-regulated by treatment not only with cloquintocet-mexyl but also with phenobarbital, which is known to stimulate xenobiotic metabolism in animals and plants. DNA sequences of five glutathione transferases (GSTs) belonging to three different classes and a multidrug resistance associated protein (MRP) homologue were identified in the screen. The chemical inducibility of these clones was confirmed by Northern analysis. The MRP protein was shown to be induced by treatments with cloquintocet-mexyl and phenobarbital and to be localised to the tonoplast. Since clodinafop-propargyl is not known to be metabolised by glutathionylation, the significance of GST induction is interpreted in terms of a generalised response to chemical stress, particularly the generation of active oxygen species. This work establishes herbicide safeners as useful tools for the identification of genes encoding herbicide-metabolising enzymes. © 2003 Society of Chemical Industry [source] The interaction of selected natural products with human recombinant glutathione transferasesPHYTOTHERAPY RESEARCH, Issue 11 2004Rose Hayeshi Abstract The interaction of geshoidin, diospyrin and ergothioneine, with heterologously expressed human glutathione transferases (GSTs) was investigated in vitro. Diospyrin and geshoidin inhibited the three GST isoforms tested, with IC50 values in the range 0.1,0.5 µm, whereas ergothioneine had no effect on the GSTs. The predominant mode of inhibition was noncompetitive with respect to both glutathione (GSH) and 1-chloro-2,4-dinitrobenzene (CDNB). Diospyrin, however, competitively inhibited A1-1 and M1-1 with respect to GSH and geshoidin displayed mixed inhibition toward A1-1 with respect to GSH. The Ki values for diospyrin with respect to both GSH and CDNB were in the range 0.08,0.6 µM and those for geshoidin were in the range 16,173 µM. These results indicate that diospyrin is a potent inhibitor of heterologously expressed human GSTs A1-1, M1-1 and P1-1. Diospyrin and geshoidin were also found to inactivate P1-1 with diospyrin being a potent inactivator. Given these inhibitory properties, diospyrin may be a potential GST chemomodulator. Ergothioneine inactivated P1-1 only after preincubation and it enhanced ethacrynic acid inactivation of P1-1. Inactivation of P1-1 by ergothioneine may have implications for the antioxidant roles of P1-1 and ergothioneine in vivo. Copyright © 2004 John Wiley & Sons, Ltd. [source] Crystallization and preliminary X-ray analysis of glutathione transferases from cyanobacteriaACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 5 2009Susanne C. Feil Glutathione S -transferases (GSTs) are a group of multifunctional enzymes that are found in animals, plants and microorganisms. Their primary function is to remove toxins derived from exogenous sources or the products of metabolism from the cell. Mammalian GSTs have been extensively studied, in contrast to bacterial GSTs which have received relatively scant attention. A new class of GSTs called Chi has recently been identified in cyanobacteria. Chi GSTs exhibit a high glutathionylation activity towards isothiocyanates, compounds that are normally found in plants. Here, the crystallization of two GSTs are presented: TeGST produced by Thermosynechococcus elongates BP-1 and SeGST from Synechococcus elongates PCC 6301. Both enzymes formed crystals that diffracted to high resolution and appeared to be suitable for further X-ray diffraction studies. The structures of these GSTs may shed further light on the evolution of GST catalytic activity and in particular why these enzymes possess catalytic activity towards plant antimicrobial compounds. [source] | |||||||||||||