Proteins have evolved to balance the structural requirements for stability with the need for specialised conformations imparting catalytic activity and ligand-binding capabilities. The glutathione transferases (GSTs) are a multi-gene family of ubiquitous proteins that are predominantly involved in the detoxification of reactive endo- and xenobiotic compounds through conjugation to the tripeptide glutathione. The family of cytosolic GSTs contain a canonical structure composed of a thioredoxin-like fold in domain 1 and an all-α-helical domain 2. Domain 1 of the cytosolic GSTs contains a highly conserved isoleucine residue in α-helix 3, located below the active site at position 71 in human class Alpha glutathione transferase A1-1 (hGST A1-1), that is involved in maintaining the packing within the hydrophobic core of domain 1. The objective of this study was to provide insight into the role of the topologically conserved Ile-71 residue in the structure, stability, and the catalytic and ...
The class of Omega glutathione transferases is newly identified with novel structural and functional characteristics. Human GSTO 1-1 (glutathione S-transferase Omega 1) is the first member of the GST Omega class. It was found to play a role in apoptosis and be in association with age-at-onset of AD and PD. In order to improve the understanding of the properties of other Omega class members, we screened a human fetal brain cDNA library and obtained the human GSTO2 (glutathione S-transferase Omega 2) cDNA. The full-length cDNA of human GSTO2 is 1179 bp long and encodes a protein of 243 amino acid residues. Expression pattern analysis revealed that GSTO2 was ubiquitously expressed at a low level, with a higher expression in pancreas and prostate. Enzyme assays showed that GSTO2 protein had activities similar to Omega class GSTs. It has detectable glutathione-dependent thiol transferase activity and glutathione-dependent dehydroascorbate reductase activity. But different from GSTO1-1, GSTO2 exhibits ...
Sappl P.G., Onate-Sanchez L., Singh K.B., Millar A.H.. Plant glutathione S -transferases (GSTs) are a large group of multifunctional proteins that are induced by diverse stimuli. Using proteomic approaches we identified 20 GSTs at the protein level in Arabidopsis cell culture with a combination of GST antibody detection, LC-MS/MS analysis of 23-30 kDa proteins and glutathione-affinity chromatography. GSTs identified were from phi, tau, theta, zeta and DHAR sub-sections of the GST superfamily of 53 members. We have uncovered preliminary evidence for post-translational modifications of plant GSTs and show that phosphorylation is unlikely to be responsible. Detailed analysis of GST expression in response to treatment with 0.01-1 mM of the plant defence signal salicylic acid (SA) uncovered some interesting features. Firstly, GSTs appear to display class-specific concentration-dependent SA induction profiles highlighting differences between the large, plant specific phi and tau classes. Secondly, ...
The glutathione S-transferases (α, μ, and π), a family of Phase II detoxication enzymes, play a critical role in protecting the colon mucosa by catalyzing the conjugation of dietary carcinogens with glutathione. We investigated the efficacy of using the glutathione S-transferase (GST) activity of blood lymphocytes and GST-μ expression as biomarkers of risk for colorectal cancer. GST activity was measured in the blood lymphocytes of control individuals (n = 67) and in the blood lymphocytes (n = 60) and colon tissue (n = 34) of individuals at increased risk for colon cancer. Total GST activity was determined spectrophotometrically with the use of 1-chloro-2,4-dinitrobenzene as a substrate. The ability to express the µ subclass of GST was determined with the use of an ELISA. Although interindividual variability in the GST activity of blood lymphocytes was greater than 8-fold (range, 16.7-146.8 nmol/min/mg), the GST activity of blood lymphocytes and colon tissue within an individual was ...
As part of my work I have to write a (pretend) grant application. Im thinking of doing something on silencing glutathione s transferase. Does anyone know of any papers or reviews on the subject of glutathione silencing. I can only find one bit of research on the sigma type and Im interested in work on all the family. please ...
TY - JOUR. T1 - The Nrf2 transcription factor regulates basal expression of class alpha and class Mu glutathione S-transferases in the mouse, but not necessarily their induction by cancer chemopreventive agents. AU - McMaghon, Michale. AU - Chanas, Simon A.. AU - Henderson, Colin J.. AU - Wolf, C. Roland. AU - Yamamoto, Masayuki. AU - Hayes, John D.. PY - 2001/2/28. Y1 - 2001/2/28. N2 - Nrf2 controls the basal expression of genes regulated through the antioxidant responsive element (ARF). It also contributes to the inducible expression of certain members of the ARE-gene battery. Under normal dietary conditions, the expression of class Alpha and class Mu glutathione S-transferase (GST) isoenzymes and NAD(P)H:quinone oxidoreductase (NQO) in the liver and small intestine is reduced significantly in nrf 2 (-/-) mice. Administration of chemopreventive agents to wildtype mice can result in marked induction of hepatic and intestinal GST and NQO. However, the extent of induction of these detoxication ...
The major glutathione S-transferase isoform of flounder liver, an antigenically related structural homologue of plaice GST-A, also displays mRNA homology. A 901bp cRNA probe for plaice GST-A cross-hybridised to a 1100bp flounder mRNA on northern blot analysis. The plaice antibody and cRNA probes were used to study effects of inducer treatment on GST-A expression in flounder liver. Six days after PAH treatment (3-methylcholanthrene) total hepatic GST activity was halved, levels of GST-A were 80% and GST-A mRNA levels were 25% of controls. A commercial PCB mixture (Aroclor 1254TM) had little effect on total GST or GST-A levels despite halving GST-A mRNA levels. An epoxide, trans-stilbene oxide induced total GST activity 1·4 fold and GST-A protein levels 1·8-fold and its mRNA levels 3-fold. This reduced expression of the major flounder hepatic GST by agents which induce cytochrome P4501A1 may modulate cytoxicity of environmental pollutants in this species. ...
The reversible reaction of GSH with two dietary anticarcinogens, benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC), has been studied in the absence and presence of human glutathione S-transferases (GSTs). The spontaneous reaction at pH 7.4 and 37 degrees C yielded values for k2 of 17.9 and 6.0 M-1.s-1 for GSH conjugation of BITC and PEITC respectively (forward reaction), and k1 values of 6.9 x 10(-4) and 2.4 x 10(-4) s-1 for dissociation of the respective GSH conjugates, BITC-SG and PEITC-SG (reverse reaction). GSTs A1-1, A2-2, M1a-1a and P1-1 catalysed both the forward and reverse reactions with specific activities (mumol/min per mg at 30 microM isothiocyanate or GSH conjugate) ranging from 23.1 for the GSH conjugation of BITC by GST P1-1 to 0.03 for the dissociation of BITC-SG by GST A1-1. When present at similar concentration to substrates (12 microM), GSTs A1-1 and A2-2 but not GST M1a-1a shifted the equilibrium in favour of BITC-SG or PEITC-SG. Kinetic studies confirmed that ...
Glutathione S-transferases (GSTs) are multifunctional detoxification enzymes that play important roles in insects. The completion of several insect genome projects has enabled the identification and characterization of GST genes over recent years. This study presents a genome-wide investigation of the diamondback moth (DBM), Plutella xylostella, a species in which the GSTs are of special importance because this pest is highly resistant to many insecticides. A total of 22 putative cytosolic GSTs were identified from a published P. xylostella genome and grouped into 6 subclasses (with two unclassified). Delta, Epsilon and Omega GSTs were numerically superior with 5 genes for each of the subclasses. The resulting phylogenetic tree showed that the P. xylostella GSTs were all clustered into Lepidoptera-specific branches. Intron sites and phases as well as GSH binding sites were strongly conserved within each of the subclasses in the GSTs of P. xylostella. Transcriptome-, RNA-seq- and qRT-PCR-based analyses
Glutathione S-transferases (GSTs) are a diverse family of phase II detoxification enzymes found in almost all organisms. Besides playing a major role in the detoxification of xenobiotic and toxic compounds, GSTs are also involved in the regulation of mitogen activated protein (MAP) kinase signal transduction by interaction with proteins in the pathway. An in vitro study was performed for Theta, Omega, Sigma GSTs and their interaction with MAP kinase p38b protein from the fruit fly Drosophila melanogaster Meigen (Diptera: Drosophilidae). The study included the effects of all five Omega class GSTs (DmGSTO1, DmGSTO2a, DmGSTO2b, DmGSTO3, DmGSTO4), all five Theta class GSTs (DmGSTT1, DmGSTT2, DmGSTT3a, DmGSTT3b, DmGSTT4), and one Sigma class glutathione transferase on the activity of Drosophila p38b, including the reciprocal effect of this kinase protein on glutathione transferase activity. It was found that DmGSTT2, DmGSTT3b, DmGSTO1, and DmGSTO3 activated p38b significantly. Substrate specificities ...
Established Fa32 cells, derived from a rat hepatoma, were investigated for their glutathione S-transferase (GST) induction capacity, which is an important characteristic of the detoxification capacity in normal liver. The cells were exposed to inducers of drug metabolism for 3 days in complete medium (containing 10% fetal calf serum). Neither dimethyl sulphoxide nor dimethyl formamide could be used as a vehicle to transport the inducers into the cells, because they also interacted with GST. Phenobarbital, butylated hydroxyanisole, allyl isothiocyanate and dimethyl fumarate (but not fumaric acid) all effectively increased the total specific GST activity. None of the test chemicals produced a very pronounced induction of specific GST subunits, but subunit 2 and subunit 8 were increased more than the others. The effects of inducers of drug metabolism on the GST activity in Fa32 cells are comparable with those in rat liver. These cells can therefore be used as a valuable alternative model for ...
Normal rat liver expresses Ya (Mr 25,500), Yc (Mr 27,500) and Yk (Mr 25,000) Class Alpha glutathione S-transferase (GST) subunits. The Ya-type subunit can be resolved into two separate polypeptides, designated Ya1 and Ya2, by reverse-phase h.p.l.c. In rat livers that possess aflatoxin B1-induced pre-neoplastic nodules, a marked increase is observed in the expression of Ya1, Ya2, Yc and Yk; of these subunits, Ya2 exhibited the greatest increase in concentration. The Ya1 and Ya2 subunits isolated from nodule-bearing livers were cleaved with CNBr, and the purified peptides were subjected to automated amino-acid-sequence analysis. Differences in the primary structures of the two Ya GST subunits were found at positions 31, 34, 107 and 117. These data demonstrate that Ya1 and Ya2 are distinct polypeptides and are the products of separate genes. The amino acid sequences obtained from Ya1 and Ya2 were compared with the cloned cDNAs pGTB 38 [Pickett, Telakowski-Hopkins, Ding, Argenbright & Lu (1984) J. ...
In humans, glutathione-dependent conjugation of halomethanes is polymorphic, with 60% of the population classed as conjugators and 40% as non-conjugators. We report the characterization of the genetic polymorphism causing the phenotypic difference. We have isolated a cDNA that encodes a human class Theta GST (GSTT1) and which shares 82% sequence identity with rat class Theta GST5-5. From PCR and Southern blot analyses, it is shown that the GSTT1 gene is absent from 38% of the population. The presence or absence of the GSTT1 gene is coincident with the conjugator (GSST1+) and non-conjugator (GSTT1-) phenotypes respectively. The GSTT1+ phenotype can catalyse the glutathione conjugation of dichloromethane, a metabolic pathway which has been shown to be mutagenic in Salmonella typhimurium mutagenicity tester strains and is believed to be responsible for carcinogenicity of dichloromethane in the mouse. In humans, the enzyme is found in the erythrocyte and this may act as a detoxification sink. ...
BACKGROUND AND OBJECTIVES: Glutathione S-transferases (GSTs) are phase II metabolizing enzymes which catalyze the conjugation of glutathione (GSH) to electrophilic substrates and possess selenium-independent glutathione peroxidase activity. The GST enzyme family includes the cytosolic isoforms GST-alpha, mu (GSTM), pi (GSTP), theta (GSTT) and sigma (GSTS). GSTT1, P1 and M1 are polymorphic and altered polymorphic frequency of genes encoding these proteins has been suggested as a potential risk factor for the development of hematopoietic malignancies. Overexpression of GSTs has also been implicated in chemotherapeutic drug resistance. This study was undertaken to elucidate the potential functional relevance of these genetic polymorphisms in hematopoiesis. DESIGN AND METHODS: GST genotype of 14 hematopoietic cell lines was determined by polymerase- chain-reaction (PCR). Gene expression of GSTs in a cell line was detected by real-time quantitative reverse transcriptase-polymerase chain reaction ...
TY - JOUR. T1 - Nitration of tyrosine 92 mediates the activation of rat microsomal glutathione S-transferase by peroxynitrite. AU - Ji, Yanbin. AU - Neverova, Irina. AU - Van Eyk, Jennifer E.. AU - Bennett, Brian M.. PY - 2006/1/27. Y1 - 2006/1/27. N2 - There is increasing evidence that protein function can be modified by nitration of tyrosine residue(s), a reaction catalyzed by proteins with peroxidase activity, or that occurs by interaction with peroxynitrite, a highly reactive oxidant formed by the reaction of nitric oxide with superoxide. Although there are numerous reports describing loss of function after treatment of proteins with peroxynitrite, we recently demonstrated that the microsomal glutathione S-transferase 1 is activated rather than inactivated by peroxynitrite and suggested that this could be attributed to nitration of tyrosine residues rather than to other effects of peroxynitrite. In this report, the nitrated tyrosine residues of peroxynitrite-treated microsomal glutathione ...
Human hepatic glutathione S-transferase (GST) subunits were characterized and quantified with the aid of a recently developed h.p.l.c. method. In 20 hepatic tissue specimens the absolute amounts of the basic Class Alpha subunits B1 and B2, the near-neutral Class Mu subunits mu and psi and the acidic subunit pi were determined. The average total amount of GST was 37 micrograms/mg of cytosolic protein, with the Class Alpha GST being the predominant class (84% of total GSTs), and pi as the sole representative of the Class Pi GSTs present in the lowest concentration (4% of total GSTs). Large interindividual differences were observed for all subunits, with variations up to 27-fold, depending on the subunit. For the Class Alpha GST-subunits B1 and B2, a biphasic ratio was observed. The genetic polymorphism of the subunits mu and psi was confirmed by h.p.l.c. analysis, and correlated with the enzymic glutathione conjugation of trans-stilbene oxide and with Western blotting of cytosols, using a ...
Bacterial glutathione transferases (GSTs; EC 2.5.1.18) are part of a superfamily of enzymes that play a crucial role in cellular detoxification. The primary role of GSTs is to catalyse the conjugation of glutathione (GSH) with the electrophilic centers of a wide variety of molecules. GSTs are widely distributed in aerobic bacteria and are classified into several classes. GSTs are not detected in anaerobic bacteria or archaea. In bacteria, GSTs are involved in a variety of distinct processes such as biotransformation of toxic compounds, protection against several stresses and antibacterial drug resistance. Glutathione Glutathione S-transferase Fosfomycin Rossjohn J, Polekhina G, Feil SC, Allocati N, Masulli M, Di Ilio C, Parker MW (1998) A mixed disulfide bond in bacterial glutathione transferase: functional and evolutionary implications. Structure 6 721-734. Hayes JD, Flanagan JU, Jowsey IR (2005). "Glutathione transferases". Annual Review of Pharmacology and Toxicology. 45: 51-88. ...
TY - JOUR. T1 - Glutathione S-transferase T1 and M1. T2 - Gene sequence variation and functional genomics. AU - Moyer, Ann. AU - Salavaggione, Oreste E.. AU - Hebbring, Scott J.. AU - Moon, Irene. AU - Hildebrandt, Michelle A T. AU - Eckloff, Bruce W.. AU - Schaid, Daniel J. AU - Wieben, Eric D. AU - Weinshilboum, Richard M. PY - 2007/12/1. Y1 - 2007/12/1. N2 - Purpose: The glutathione S-transferases (GSTs) catalyze the glutathione conjugation of reactive electrophiles, including carcinogens and many antineoplastic drugs. GSTT1 and GSTM1 are polymorphically deleted, but the full range of genetic variation in these two genes has not yet been explored. We set out to systematically identify common polymorphisms in GSTT1 and GSTM1, followed by functional genomic studies. Experimental Design: First, multiplex PCR was used to determine GSTT1 and GSTM1 copy number in 400 DNA samples (100 each from 4 ethnic groups). Exons, splice junctions, and 5′-flanking regions (5′-FR) were then resequenced using ...
Sparnins, V L. and Wattenberg, L W., "Enhancement of glutathione s-transferase activity of the mouse forestomach by inhibitors of benzo[a]pyrene-induced neoplasia of the forestomach." (1981). Subject Strain Bibliography 1981. 2170 ...
TY - JOUR. T1 - Characterization of a class alpha glutathione-S-transferase with glutathione peroxidase activity in human liver microsomes. AU - Prabhu, Kumble Sandeep. AU - Reddy, Padala V.. AU - Jones, Emily C.. AU - Liken, Andrew D.. AU - Reddy, C. Channa. PY - 2004/4/1. Y1 - 2004/4/1. N2 - A 25.5kDa class alpha glutathione S-transferase (GST) designated as microsomal Ya-GST or M-GSTA has been purified to electrophoretic homogeneity from human liver microsomes. Limited proteolysis, gel filtration chromatography followed by EDTA, and alkaline Na2CO3 treatments of microsomes indicate that the M-GSTA is intrinsic to the microsomes. Western immunoblot analysis revealed that human liver M-GSTA and the previously reported 17-kDa microsomal GST (FEBS Lett. 315 (1993) 77) did not have immunological cross reactivity. The enzyme showed conjugation activity towards substrates like 1-chloro-2,4-nitrobenzene (CDNB) and 7-chloro-4-nitrobenzo-2- oxa-1,3-diazole, and 4-hydroxy-2-nonenal (4-HNE), a genotoxic ...
TY - JOUR. T1 - Effect of glutathione-S-transferase M1 and T1 allelic polymorphisms on HPV-induced cervical precancer formation. AU - Cseh, József. AU - Pázsit, Emese. AU - Orsós, Zsuzsa. AU - Marek, Erika. AU - Huszár, András. AU - Balogh, Sándor. AU - Ember, I.. AU - Kiss, István. PY - 2011/9. Y1 - 2011/9. N2 - Aim: The effect of GSTM1 and GSTT1 allelic polymorphisms was studied on the HPV-induced cervical carcinogenesis. Patients and Methods: Two hundred and fifty-three women with persistent high-risk HPV infection were involved in the study; 117 of them developed cervical high-grade dysplasia and/or cervical intraepithelial neoplasia grade III during the 7-year follow-up period. Occurrence of GSTM1 and GSTT1 null genotypes was compared between women with and without dysplasia. Results: Presence of GSTM1 (OR=1.78, 95% CI=1.06-2.97; p=0.028) and GSTT1 (OR= 1.89, 95% CI=1.10-3.26; p=0.022) null genotypes was statistically significantly more frequent among women with cervical dysplasia ...
Cruciferous vegetables, especially broccoli, may prevent cancer through anticarcinogenic compounds. For example, broccoli contains isothiocyanates that induce carcinogen-detoxifying enzymes. Glutathione transferase enzymes conjugate isothiocyanates, leading to excretion. We hypothesized that broccoli consumption in combination with the glutathione transferase M1 (GSTM1) null genotype would be associated with a lower prevalence of colorectal adenomas because of higher isothiocyanate levels. We used a case-control study of mainly asymptomatic subjects aged 50-74 years who underwent a screening sigmoidoscopy at either of two Southern California Kaiser Permanente Medical Centers during 1991-1993. Cases (n = 459) had a first-time diagnosis of histologically confirmed adenomas detected by flexible sigmoidoscopy. Controls (n = 507) had no polyp detected. Subjects had a 45-min in-person interview for information on various risk factors and basic demographic data and completed a 126-item, ...
Alpha-class glutathione transferases (GSTs) found expressed in human tissues constitute a family of four homologous enzymes with contrasting enzyme activities. In particular, GST A3-3 has been shown to contribute to the biosynthesis of steroid hormones in human cells and is selectively expressed in steroidogenic tissues. The more ubiquitous GST A1-1, GST A2-2, and GST A4-4 appear to be primarily involved in detoxification processes and are expressed at higher levels than GST A3-3. We are interested in studying the cell and tissue expression of the GST A3-3 gene, yet the existence of highly expressed sequence-similar homologs and of several splice variants is a serious challenge for the specific detection of unique transcript species. We found that published polymerase chain reaction (PCR) primers for GST A3-3 lack the specificity required for reliable quantitative analysis. Therefore, we designed quantitative PCR (qPCR) primers with greatly increased discrimination power for the human GSTA3 ...
TY - JOUR. T1 - Host genetic variations in glutathione-S-transferases, superoxide dismutases and catalase genes influence susceptibility to malaria infection in an Indian population. AU - Fernandes, Rayzel C.. AU - Hasan, Marriyah. AU - Gupta, Himanshu. AU - Geetha, K.. AU - Rai, Padmalatha S.. AU - Hande, Manjunath H.. AU - DSouza, Sydney C.. AU - Adhikari, Prabha. AU - Brand, Angela. AU - Satyamoorthy, Kapaettu. PY - 2015/6/23. Y1 - 2015/6/23. N2 - Antioxidant enzymes can contribute to disease susceptibility or determine response to therapy in individuals with malaria. Genetic variations due to polymorphisms in host genes encoding antioxidant enzymes such as glutathione S-transferases-theta, mu, pi (GSTT, GSTM, GSTP), superoxide dismutases (SOD) and catalase (CAT), may therefore, influence inter-individual response to malaria pathology and propensity of infection caused by Plasmodium vivax (Pv) and Plasmodium falciparum (Pf). Therefore, using polymerase chain reaction-restriction fragment ...
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Genetic polymorphisms constitute one of the reasons behind the racial variation in prostate cancer occurrence. Published studies regarding genetic associations of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) null deletion polymorphisms with prostatic carcinoma have generated inconsistent results among different populations. To date, even a single meta-analysis is not available representing the association of these genes with prostate cancer in different ethnic groups. Therefore, the aim of the current study was to provide a clear picture of GSTM1 and GSTT1 null deletion and risk of prostate cancer among different ethnic groups (i.e. Asians, Europeans, Americans, Africans and Eurasians). A systematic search was performed with the help of various search engines to find out the all the recent studies (2004 to 2015) evaluating the role of GSTM1 and GSTT1 deletion in prostate cancer development. Odds ratios (ORs) with 95% confidence interval (CI) of a total of 34
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Recombinant human GSTM5 protein, fused to His-tag at N-terminus, was expressed in E. coli and purified by using conventional chromatography techniques.
This thesis describes how the human Alpha class glutathione transferase (GST) A1-1 can be reprogrammed either to function as a multipurpose biosensor for detection of small molecule analytes, or as a handle providing for more efficient protein purification.A novel, user-friendly, and efficient method for site-specific introduction of functional groups into the active site of hGST A1-1 is the platform for these achievements. The designed thioester reagents are glutathione-based and they are able to label one single nucleophile (Y9) and leave the other 50 nucleophiles (in hGST A1-1) intact. The modification reaction was tested with five classes of GSTs (Alpha, Mu, Pi, Theta and Omega) and was found to be specific for the Alpha class isoenzymes. The reaction was further refined to target a single lysine residue, K216 in the hGST A1-1 mutant A216K, providing a stable amide bond between the protein and the labeling group. To further improve the labeling process, biotinylated reagents that could ...
An association of lung cancer susceptibility with an MspI restriction site polymorphism of the CYP1A1 gene was reported in our previous study. This polymorphism has been subsequently found to be closely linked to another isoleucine-valine (Ile-Val) polymorphism, which resulted in an Ile-Val amino acid replacement in the heme-binding region of P4501A1.. We report here that genetic risk for squamous cell carcinoma of the lung was associated with these two polymorphisms of the CYP1A1 gene in terms of genotype frequencies and cigarette-smoking dose and that a more increased risk was observed for the individuals with "susceptible" genotypes of CYP1A1 combined with a deficient genotype of a µ-class glutathione S-transferase (GST1), which detoxifies the electrophilic metabolites of aromatic hydrocarbon procarcinogens activated by P4501A1. We first compared the total amounts of cigarettes consumed during a lifetime among 85 patients with squamous cell carcinoma of the lung, whose CYP1A1 and GST1 genes ...
Several lines of evidence correlate the overexpression of glutathione S-transferase omega 1-1 (GSTO1-1) with the onset of drug resistance of cancer cells; however, no direct evidence is yet available. In order to investigate the mechanisms involved, stable transfection with GSTO1-1 complementary DNA was performed in HeLa cells, which spontaneously express very low levels of GSTO1-1. When transfected cells were seeded at low density, a sharp increase in GSTO1-1 expression was observed as compared with controls, along with an increased resistance against cisplatin cytotoxicity. When seeded at increasing densities, control untransfected cells also presented with an increase in GSTO1-1 expression, again accompanied by cisplatin resistance; the latter was significantly reduced after transfection with GSTO1-1 small interfering RNA. Cisplatin resistance of transfected cells was not accounted for by changes in the intracellular drug concentration nor in the amount of DNA cross-links or content of ...
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The null genotype of GSTM1 have been implicated in gastric cancer risk, but numerous individual studies showed mixed, or even conflicting results. Thus, a meta-analysis was performed. We identified 54 individual studies involving 9,322 cases and 15,118 controls through computer-based searches of PubMed, Embase, and Cochrane Library. It was found that the null genotype of GSTM1 was associated with an increased gastric cancer risk (OR = 1.207, 95% CI: 1.106-1.317, P | 0.001), under the random-effects model (I2 : 49.9%, PQ |0.001). From stratification analyses for ethnicity, alcohol drinking, Helicobacter pylori infection, an effect modification of gastric cancer risk was found in the subgroups of ethnicity, smoking status, Helicobacter pylori infection, whereas null result was found in the subgroups of alcohol drinking. We also undertook gene-gene interaction analysis between GSTM1 and GSTT1 genes for gastric cancer risk, and the results indicated that the dual null genotypes of GSTM1 and GSTT1 might
1HNB: Crystal structure of human class mu glutathione transferase GSTM2-2. Effects of lattice packing on conformational heterogeneity.
The addition of pyruvate to the culture medium has been reported to improve the maintenance of P450-dependent enzyme expression in primary rat hepatocyte cultures. In this study, the effects of 30mM pyruvate on cell morphology, albumin secretion and glutathione Stransferase (GST) expression were investigated as a function of the time in culture. The effect of triiodothyronine (T3) exposure on GST expression was also measured in pyruvate-treated cultures. Transmission electron microscopy showed that untreated hepatocytes deteriorated after culture for 7 days, whereas the morphology of the pyruvate-treated cells was similar to that observed in intact liver tissue. The albumin secretion rate was significantly higher in rat hepatocytes exposed to pyruvate than in control cells. In the presence of pyruvate, μ and α class GST activities were well maintained, whereas GST π activity was increased over the entire culture period. HPLC analysis revealed that the complement of GST subunits present in ...
1GLP: Molecular structure at 1.8 A of mouse liver class pi glutathione S-transferase complexed with S-(p-nitrobenzyl)glutathione and other inhibitors.
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Cancer is widely accepted as one of the major health issues. Diet composition and exposure to environmental genotoxic and carcinogenic agents such as polycyclic aromatic hydrocarbons (PAHs) are among the causative factors for various types of cancers, including breast cancer. Low penetrance genes including glutathione S transferases (GST) in association with environmental factors can contribute greatly in the development of breast cancer. We were interested to investigate the association of the polymorphisms of GSTM1, GSTT1, GSTP1 and GSTO2 with the risk of breast cancer in the Pakistani population. One hundred women visiting the Department of Radiology and Oncology, Nishter Hospital, Multan with pathologically confirmed breast cancer, and 100 healthy volunteers from central Pakistan were enrolled in the present study. The strength of the association of various factors with breast cancer was measured by calculating odd ratios (ORs) which were determined by logistic regression. All P values cited ...
Glutathione (GSH) is a compound synthesized from cysteine. Like cysteine, glutathione contains the crucial thiol (-SH) group that makes it an effective antioxidant. There are virtually no living organisms on this planet-animal or plant whose cells dont contain some glutathione. Scientists have speculated that glutathione was essential to the very development of life on earth. Glutathione has many roles; in none does it act alone. It is a coenzyme in various enzymatic reactions. The most important of these are redox reactions, in which the thiol grouping on the cysteine portion of cell membranes protects against peroxidation; and conjugation reactions, in which glutathione binds with toxic chemicals in order to detoxify them. GSH is known as a substrate in both conjugation reactions and reduction reactions, catalyzed by glutathione S-transferase enzymes in the bacterial cytosol ...
KUHNERT, Diane C.; GILDENHUYS, Samantha y DIRR, Heini W.. Effect of macromolecular crowding on the stability of monomeric glutaredoxin 2 and dimeric glutathione transferase A1-1. S. Afr. j. sci. [online]. 2008, vol.104, n.1-2, pp.76-80. ISSN 1996-7489.. The effect of macromolecular crowding on the structure and stability of monomeric glutaredoxin 2 (Grx2) and its homodimeric structural homologue human glutathione transferase A1-1 (hGST A1-1) was investigated using dextran 70 as crowding agent. Far-UV circular dichroism and fluorescence spectroscopic data indicated that repulsive steric interactions between the proteins and dextran (50-300 mg/ml) had little effect on the global structures of the native proteins. Urea-induced unfolding of both proteins was reversible (recoveries of ,80%) at low dextran concentrations (,100 mg/ml) but resulted in significant losses in refolding recoveries at higher levels of dextran, due to aggregation. The two-state global unfolding processes of Grx2 and hGST ...
Glutathione transferase genes (GST) are candidate genes for Parkinsons disease because they are involved with the metabolism of pesticides, dopamine, and glutathione. Recent reports have suggested an association between Parkinsons disease and polymorphisms of GSTP1 1 orGSTM1 andGSTT1.2 Recently we discovered a new polymorphic site in the zeta class G→T (GSTZ1) gene.3 This consists of a C6T transition at nucleotide 245 in exon 5 that results in an amino acid change at position 82 from methionine to threonine. The T substitution occurs in 14% of white people. We have previously reported two other polymorphic sites at nucleotides 94 and 124 in exon 3.4 There are now thought to be four alleles of GSTZ1:Z1*A(A94A124C245),Z1*B(A94G124C245),Z1*C(G94G124C245,) andZ1*D(G94G124T245). Here we investigated the association of Parkinsons disease, pesticide exposure, and theseGSTZ1 polymorphisms.. DNA was extracted from blood samples collected from patients with Parkinsons disease and matched controls as ...
Detoxification of plant toxins is a necessity for most herbivorous insects to successfully feed on their host plants. The cabbage stem flea beetle Psylliodes chrysocephala is a serious pest of many Brassicaceae. These plants produce glucosinolates, which are converted to toxic isothiocyanates upon tissue damage. A recent study on the metabolic fate of 4-methylsulfinylbutyl (4MSOB) glucosinolate in P. chrysocephala has shown that P. chrysocephala uses different ways to cope with this plant defense compound. Besides sequestration of intact glucosinolates and the production of desulfo-glucosinolates, P. chrysocephala metabolizes toxic isothiocyanates by conjugation to glutathione via the conserved mercapturic acid pathway. In this project I will investigate the role of glutathione S -transferases in the detoxification of isothiocyanates in P. chrysocephala ...
the target sequences for human Epac1 siRNA mixture have been. sense. 53, sense. 53, sense. 53, sense. 53 and for that Epac2 siRNA mixture. sense. 53, sense. 53, MK-2048 sense. 53, sense. 53. Non silencing siRNA control was utilized as a handle in all siRNA transfection experiments. Cells were transfected with 200 pmol of suitable siRNA through the use of lipofectamine 2000 as vehicle. 6 hrs immediately after transfection, cells had been washed with DMEM supplemented with antibiotics to cut back toxicity results on the transfection reagent. Cells have been subsequently analyzed for Epac1 and Epac2 expres sion, GTP loading of Rap1 or IL 8 production. Activation of Rap1, phosphorylation of ERK1/2 VASP and immunoblot evaluation The quantity of activated Rap1 and Rap2 was measured with the pull down method by utilizing glutathione S transferase tagged RalGDS as previously described. To the measurement with the phosphorylation of ERK1/2 and VASP, cell had been lysed fol lowed by determination within ...
We compared the pattern of gene category overrepresentation in each gene set using the expression analysis systematic explorer (EASE) application (Hosack et al, 2003) (full data in Supplementary Data Set S1). As expected, Sets A and B showed enrichment of class 1, a set of genes independently defined as upregulated in long‐lived IIS mutants (Murphy et al, 2003), but Set C did not (Figure 3B), confirming that few of the genes in Set C are IIS/DAF‐16 regulated. Previous studies have shown upregulation by DAF‐16 of many drug metabolizing enzymes (DMEs), for example cytochrome P450 oxidases and glutathione S‐transferases (McElwee et al, 2007). These categories are not enriched among Sets B or C but are enriched in Set A (Figure 3B), suggesting that DAF‐16 upregulation of DMEs is indirect.. Given that they show both IIS/DAF‐16 regulation and DAF‐16 binding, the 65 genes in Set B represent high‐confidence DAF‐16 regulatory targets (Supplementary Table SII; Supplementary Figure S3). ...
Aim: The incidence of stomach cancer in Mizoram is highest in India. We have conducted a populationbased matched case-control study to identify environmental and genetic risk factors in this geographical area.Methods: A total of 102 histologically confirmed stomach cancer cases and 204 matched healthy populationcontrols were recruited. GSTM1 and GSTT1 genotypes were determined by PCR and H. pylori infections weredetermined by ELISA. Results: Tobacco-smoking was found to be an important risk factor for high incidenceof stomach cancer in Mizoram. Meiziol (local cigarette) smoking was a more important risk factor than othertobacco related habits. Cigarette, tuibur (tobacco smoke infused water) and betel nut consumption synergisticallyincreased the risk of stomach cancer. Polymorphisms of GSTM1 and GSTT1 genes were not found to be directlyassociated with stomach cancer in Mizoram. However, they appeared to be effect modifiers. Persons habituatedwith tobacco smoking and/or tuibur habit had increased risk of
The Gene Ontology (GO) project is a collaborative effort to address the need for consistent descriptions of gene products across databases. You can use this browser to view terms, definitions, and term relationships in a hierarchical display. Links to summary annotated gene data at MGI are provided in Term Detail reports.
Increased levels of alpha-class and pi-class glutathione S-transferases in cell lines resistant to 1-chloro-2,4-dinitrobenzene ...
Aim: The current study was conducted to investigate the effect of GSTP1 codon 105 polymorphism, alone and in combination with GSTM1-deletion polymorphism, on erythrocyte GST activity in 196 Han Chinese. Methods: GST activity was measured in healthy Chinese by a spectrophotometric method (n = 196; 101 males and 95 females; age range 21-81 years; median 43.5 years). GSTM1 polymorphisms were analyzed by a PCR-Multiplex procedure, whereas GSTP1 polymorphism was analyzed by PCR-RFLP. Results: The frequency of GSTM1 null genotype was 56.1% and the frequency of I/I, I/V, and V/V genotypes was 60.7%, 35.2% and 4.1%, respectively, in Han Chinese. The mean erythrocyte GST enzyme activity for I/V genotype group(3.53 ± 0.63 U · g-1 Hb) was significantly lower than that for I/I genotypes (4.25 ± 1.07 U · g-1 Hb, P = 0.000), while significantly higher than that for V/V genotypes (2.44 ± O. 67 U · g-1 Hb, P = 0.004). In GSTM1 (-) group, the GST activity of carriers of GSTM1 (-)/ GSTP1 - I/I is ...