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)

Acute allograft rejection (ARE) is one of the most current problem in kidney transplantation. Urinary enzymes (glutathione-S-transferase /GST/. dipeptidil-dipeptidase /DPP/) are frequently used as prognostic factors of ARE. The authors compared the results of light microscopic study (by Banff scheme), and the GST, and DPP secretion in acute rejection. The correlation between the laboratory, and histology findings wasn't significant. our results suggest that both GST, and DPP are very sensitive, but less specific indicators in ARE, since their activity increases in many other damages as well.
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PMID:Evaluation of urinary enzymes in renal allograft damages by histology examination. 940 65

We studied the patterns of within- and between-population variation at 29 trinucleotide loci in a random sample of 200 healthy individuals from four diverse populations: Germans, Nigerians, Chinese, and New Guinea highlanders. The loci were grouped as disease-causing (seven loci with CAG repeats), gene-associated (seven loci with CAG/CCG repeats and eight loci with AAT repeats), or anonymous (seven loci with AAT repeats). We used heterozygosity and variance of allele size (expressed in units of repeat counts) as measures of within-population variability and GST (based on heterozygosity as well as on allele size variance) as the measure of genetic differentiation between populations. Our observations are: (1) locus type is the major significant factor for differences in within-population genetic variability; (2) the disease-causing CAG repeats (in the nondisease range of repeat counts) have the highest within-population variation, followed by the AAT-repeat anonymous loci, the AAT-repeat gene-associated loci, and the CAG/CTG-repeat gene-associated loci; (3) an imbalance index beta, the ratio of the estimates of the product of effective population size and mutation rate based on allele size variance and heterozygosity, is the largest for disease-causing loci, followed by AAT- and CAG/CCG-repeat gene-associated loci and AAT-repeat anonymous loci; (4) mean allele size correlates positively with allele size variance for AAT- and CAG/CCG-repeat gene-associated loci and negatively for anonymous loci; and (5) GST is highest for the disease-causing loci. These observations are explained by specific differences of rates and patterns of mutations in these four groups of trinucleotide loci, taking into consideration the effects of the past demographic history of the modern human population.
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PMID:Rate and directionality of mutations and effects of allele size constraints at anonymous, gene-associated, and disease-causing trinucleotide loci. 1048 72

Reduced glutathion (GSH) content and glutathione S-transferase (GSH S-transferase) activity were investigated in developing toad embryos exposed to parathion, malathion, lindane and dieldrin. The embryonic GSH content was reduced after 96 h of incubation with 20.00 ppm malathion and 2.00 ppm lindane. Parathion and dieldrin did not produce any change. A similar effect was obtained in advanced stages of development (6-days larvae), but only with malathion. No correlation between the decrease in GSH level and mortality or morphologic abnormalities was observed. The four pesticides increased the activity of GSH S-transferase indicating that the enzyme is susceptible to induction during early development. The higher effect depicted by malathion may be related with an enhanced conjugation of the pesticide. Both GSH decrease and GSHS-transferase induction modifies the cell redox status and may indirectly influence transcription and translation. The early expression of GST genes provides the embryo with a useful mechanism for the regulation of tolerance against chemical stress.
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PMID:The role of glutathion conjugation in the regulation of early toad embryos' tolerance to pesticides. 1116 72

The regulator of immunoglobulin expression Oct-2 and the related widely expressed transcription factor Oct-1 have been shown to interact with DNA sequences containing an "octamer" motif, ATGC(A/T)AAT. To better understand Oct-2 function we have used random oligonucleotide selection and competition assays to define the optimal recognition site for this protein. The selected site contains an extended sequence that is remarkably similar to octamer-heptamer sequences found in immunoglobulin heavy-chain regulatory sequences, and the affinity of Oct-2 for this site is at least 50-fold greater than for sites containing the octamer motif alone. Fusion to glutathione S-transferase, a widely used model for protein-DNA and protein-protein interaction, does not alter the optimal Oct-2 recognition site, but inhibits Oct-2 POU-domain dimerization, slows the dissociation rate of the GST-Oct-2/DNA complex, and increases the relative importance of the heptamer domain for Oct-2 binding. These data advance our ability to identify in vivo targets of POU-factor regulation and also suggest that GST-fusion proteins should be used with caution in DNA-binding studies.
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PMID:Optimal Oct-2 affinity for an extended DNA site and the effect of GST fusion on site preference. 1136 23

By searching the human genome sequence database with human hGSTA1 and hGSTA4 cDNA sequences, we identified three PAC and one BAC clones covering more than 400 kilobases and containing the entire GST alpha gene cluster. The cluster consists of five genes: hGSTA1, hGSTA2, hGSTA3, hGSTA4 and hGSTA5, and seven pseudogenes that are distinguished as such by single-base and/or complete exon deletions. Using gene-specific probes we demonstrated that hGSTA1, hGSTA2 and hGSTA4 mRNAs are widely expressed in human tissues, whereas hGSTA3 mRNA appears to be a rare message subject to splicing defects. Although examination of the hGSTA5 gene sequence suggests that it is a functional gene, hGSTA5 mRNA could not be detected in human tissues we studied. hGSTA1 expression has been shown to be influenced by a genetic polymorphism, that consists of two alleles hGSTA1*A and hGSTA1*B, containing three linked base substitutions in the proximal promoter, at positions -567, -69 and -52. Constructs consisting of the luciferase gene controlled by variant hGSTA1 promoters showed differential expression when transfected into HepG2, GLC4 and Caco-2 cells: hGSTA1*A > hGSTA1*B. Directed mutagenesis for each base substitution indicated that the base change -52G>A was responsible for the differential promoter activity of hGSTA1*A and hGSTA1*B. The base at position -52 also altered binding of the ubiquitous transcription factor Sp1, as determined by gel shift analysis. Thus it may be postulated that hGSTA1 genotyping will be of importance to determine individual susceptibility to certain cancers or the efficacy of chemotherapeutics via its effect on hGSTA1 expression.
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PMID:The human glutathione transferase alpha locus: genomic organization of the gene cluster and functional characterization of the genetic polymorphism in the hGSTA1 promoter. 1204 64

The PAC(1), VPAC(1) and VPAC(2) receptors are members of the secretin (Group II) family of G protein-coupled receptors. All members of this family activate adenylate cyclase and several have also been shown to activate phospholipase C. We have recently reported that the rat VPAC(1), VPAC(2) and PAC(1) receptors activate phospholipase D and that distinct pathways are utilised by two intracellular loop 3 splice variants of PAC(1), one of which is ARF-dependent. Phospholipase D activation by the hop1, but not the null (short), form of the PAC(1) receptor is sensitive to brefeldin A, an inhibitor of GTP exchange at ARF. We have expressed the null and hop1 intracellular loop 3 domains of the human PAC(1) receptor in bacteria as GST-fusion proteins and used them as peptide affinity matrices to determine whether a functional interaction exists between these domains and ARF. Using this GST pull-down assay, we have shown binding of the small G protein ARF6 to the hop1 but not the null domain of this receptor.
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PMID:Specific interaction between the hop1 intracellular loop 3 domain of the human PAC(1) receptor and ARF. 1240 33

Polymorphisms in glutathione S-transferases (GSTs) may predispose to lung cancer through deficient detoxification of carcinogenic or toxic constituents in cigarette smoke, although previous results have been conflicting. Three GST polymorphisms (GSTM1, GSTT1 and GSTP1) were determined among 86 male patients with lung carcinomas and 88 healthy male subjects. We found no significant increase in the risk of lung cancer for any genotypes for the nulled GSTM1 [odds ratio (OR)=2.0; 95% confidence interval (95% CI)= 0.8-5.3], the nulled GSTT1 (OR=2.0; 95% CI=0.8-5.1) or the mutated (the presence of a Val-105 allele) GSTP1 (OR=0.96; 95% CI=0.4-5.5). The GST polymorphisms alone may thus not be associated with susceptibility to lung carcinogenesis in male Japanese. However, individuals with a concurrent lack of GSTM1 and GSTT1 had a significantly increased risk (OR=2.7; 95% CI=1.0-7.4) when compared with those having at least one of these genes. No other combinations were associated with lung cancer risk. These results suggest that there may be carcinogenic intermediates in cigarette smoke that are substrates for both GSTM1 and GSTT1 enzymes and that lung cancer risk is increased for individuals who are doubly deleted at GSTM1 and GSTT1 gene loci. Additional large studies are needed to confirm this observation.
Asian Pac J Cancer Prev 2000
PMID:Polymorphism in GSTM1, GSTT1, and GSTP1 and Susceptibility to Lung Cancer in a Japanese Population. 1271 3

The effects of different patterns of alcohol administration on hepatocarcinogenesis induced by diethylnitrosamine (DEN) in male Wistar rats were assessed using a modified Ito's medium-term bioassay system. Carcinogenic potential was scored by comparing numbers and areas of glutathione S transferase placental form (GST-P)-positive foci. The activity of ornithine decarboxylase (ODC), the rate-limiting enzyme for polyamine synthesis, was also measured as a parameter of cell proliferation. Rats were given a single i.p. injection of DEN (200 mg/kg body weight), maintained on basal solid diet for two weeks, then divided into five groups: group A maintained on liquid diet in which 36% of total calories were provided by ethanol (diet Al) for 24 weeks; group B maintained on diet Al for 12 weeks and subsequently on control diet (diet C) for 12 weeks; group C maintained on diet C for 24 weeks; group D maintained on a cycle of two days on diet Al followed by two days on diet C; group E maintained on another liquid diet in which 18% of total calories were provided by ethanol for 24 weeks. The numbers and areas per cm2 of GST-P positive foci in group B were highest and in group D were the lowest among the five groups. ODC activities in groups A and E were significantly lower than in group C, that for group B was intermediate. These results suggest that the intermittent intake of alcohol exerts preventive potential on hepatocellular lesion development, and that interruption of long-term alcohol administration enhances hepatocarcinogenesis.
Asian Pac J Cancer Prev 2000
PMID:Cessation of Long-term Alcohol Administration and Two-day Cycling of Exposure Respectively Promote and Inhibit Hepatocarcinogenesis in Rats. 1271 8

Allele frequencies are rather constant among different ethnic groups in many genetic polymorphisms, but some polymorphisms vary in the allele frequency depending on the time when the germ-line base exchanges occurred in the history of humans and on the adaptability of the phenotypes to given environment. This review documented the allele frequencies of polymorphisms pertaining to cancer risk for Japanese, Koreans, and Chinese. Twenty-five polymorphisms of 21 genes whose allele frequencies were available for at least two out of the three ethnic groups were selected. They were ALDH2 Glu487Lys, COMT Val158Met, CYP1A1 MspI and Val/Ile, CYP1B1 Leu432Val, CYP2E1 RsaI, CYP17 T-34C, ER C975G, GSTM1, GSTT1, GSTP1 Ile105Val, IL-1B C-511T, IL-1RN 86-bp VNTR (variable number of tandem repeats), MTHFR C677T and A1298C, NAT1, NAT2, NQO1 Pro187Ser, OGG1 Ser326Cys, p21 Ser31Arg, p53 Arg72Pro, TNF-A G-308A and G-238A, and XRCC1 Arg194Trp and Arg399Gln. The allele frequencies were found for 24 in Japanese, 16 in Koreans, and 24 in Chinese. All of the polymorphisms had similar allele frequencies for these ethnic groups, except the following polymorphisms; ALDH2 Glu487Lys whose Lys allele was more common for Japanese and Taiwanese, COMT Val158Met whose Met allele was more common for Japanese, and NAT2 rapid/slow whose slow alleles were more common for Chinese. When compared with the allele frequencies among Caucasians, the following minor alleles were more frequent among Japanese/Koreans/Chinese; ALDH2 478Lys, CYP1A1 m1 and m2, CYP2E1 c2, ER 975G, GSTT1 null, NAT1 *10, NQO1 187Ser, OGG1 326Cys, p21 31Arg, and XRCC1 194Trp, and less frequent in COMT 158Met, GST-P1 105Val, IL-1RN non-4R, MTHFR 1298C, and TNF-A -308A. The differences in genetic background may affect the impact on the lifestyle factors and/or genotypes examined in epidemiological studies. However, the influences of the variations in the allele frequency seemed to be limited among Japanese, Koreans, and Chinese. The substantial differences in the allele frequency from Caucasians could modify the influences of lifestyle factors and polymorphism genotypes, resulting in the inconsistent results of epidemiologic studies.
Asian Pac J Cancer Prev 2002
PMID:Allele Frequencies of 25 Polymorphisms Pertaining to Cancer Risk for Japanese, Koreans and Chinese. 1271 76

In recent years, numerous reports have been published on the identification of novel, naturally occurring antioxidants from plants, animals, microbial sources and processed food products. Most natural antioxidants are phenolic compounds, which have a modulatory role on physiological functions and biotransformation reactions involved in the detoxification process, thereby affording protection from cytotoxic, genotoxic and metabolic actions of environmental toxicants. As part of our program on evaluation of food, beverage and traditional medicinal plants for their anticarcinogenic activity, the present report deals with the evaluation of aqueous infusion of Black tea (Camellia sinensis), Black tea extract (80% Theaflavins) & EGCG on mice exposed to the chemical carcinogen DMBA. All the four detoxification enzymes studied viz, GST, GPx, SOD and CAT were found to be activated to different degrees following treatment with black tea and two of its active compounds. The activation of the enzymes was accompanied by significant reduction in lipid peroxidation. The effect on apoptosis and cell proliferation was also studied in mice skin following administration of DMBA. Theaflavins, and EGCG significantly inhibited cell proliferation and induced apoptosis. The observation suggests chemopreventive potential of black tea infusion, black tea extract Theaflavins and the compound EGCG.
Asian Pac J Cancer Prev 2002
PMID:Elimination of Deleterious Effects of Free Radicals in Murine Skin Carcinogenesis by Black Tea Infusion, Theaflavins & Epigallocatechin Gallate. 1271 79


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