Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nucleotide sequence of a cloned 2.8-kilobase-pair BamHI-PstI fragment containing dcmA, the dichloromethane dehalogenase structural gene from Methylobacterium sp. strain DM4, was determined. An open reading frame with a coding capacity of 287 amino acids (molecular weight, 37,430) was identified as dcmA by its agreement with the N-terminal amino acid sequence, the total amino acid composition, and the subunit size of the purified enzyme. Alignment of the deduced dichloromethane dehalogenase amino acid sequence with amino acid sequences of the functionally related eucaryotic glutathione S-transferases revealed three regions containing highly conserved amino acid residues and indicated that dcmA is a member of the glutathione S-transferase supergene family. The 5' terminus of in vivo dcmA transcripts was determined by nuclease S1 mapping to be 82 base pairs upstream of the GTG initiation codon of dcmA. Despite a putative promoter sequence with high resemblance to the Escherichia coli -10 and -35 consensus sequences, located at an appropriate distance from the transcription start point, dcmA was only marginally expressed in E. coli. The strong induction of dichloromethane dehalogenase in Methylobacterium sp. by dichloromethane was abolished by deleting the 1.3-kilobase-pair upstream region of dcmA. Plasmid constructs devoid of this region directed expression of dichloromethane dehalogenase at a constitutively induced level.
 ...
PMID:Sequence analysis and expression of the bacterial dichloromethane dehalogenase structural gene, a member of the glutathione S-transferase supergene family. 210 2

Pretreatment of Fischer 344 rats with the antioxidant ethoxyquin (EQ), followed by administration of aflatoxin B1 (AFB1) in the continuing presence of EQ was used to examine the effect of the antioxidant on liver and kidney. EQ (0.5% in diet) completely prevented the formation of AFB1-induced preneoplastic liver lesions as judged by morphological alteration, or by markers such as gamma glutamyl transpeptidase, glutathione S-transferase P or J1, an unknown membrane-bound antigen. While protection was afforded to the liver, EQ alone caused severe damage to the kidney. Many changes were those of chronic glomerulonephrosis, such that EQ appeared to accelerate the ageing process. In addition, many hyperplastic and putative preneoplastic tubules were visible, suggesting that EQ may be exerting a carcinogenic effect in the kidney.
 ...
PMID:Ethoxyquin alone induces preneoplastic changes in rat kidney whilst preventing induction of such lesions in liver by aflatoxin B1. 288 50

Female rats were subjected to a 70% partial hepatectomy and administered either diethylnitrosamine (10 mg/kg) or the solvent, trioctanoin. After a 2 day recovery from the surgery, the rats were placed on basal diet alone or containing phenobarbital (500 mg/kg diet), mestranol (0.2 mg/kg diet), tamoxifen (250 or 500 mg/kg diet) or toremifene (250, 500 or 750 mg/kg diet) for 6 or 18 months prior to killing. The liver and kidneys were prepared for pathological diagnoses. In addition, sections of liver from the 6 month killing were frozen and serially sectioned. The sections were stained for expression of the placental isozyme of glutathione S-transferase (GST), gamma glutamyl transpeptidase (GGT), canalicular ATPase (ATP) and glucose 6-phosphatase (G6P) and scored by quantitative stereology for number and volume fraction of liver occupied by altered hepatic foci (AHF) with alterations in these markers individually and combined (ANY). Each of the agents increased the volume fraction of liver occupied by AHF when the ANY category was used. Statistical increases in both the GGT-positive and G6P-deficient AHF populations were observed in the spontaneously as well as DEN-initiated groups treated with tamoxifen or toremifene. After 18 months of administration, the highest concentration of tamoxifen increased the incidence of malignant hepatic neoplasms in non-DEN-initiated rats. Toremifene, at the highest tested dose, increased the incidence of hepatocellular carcinomas in the DEN-initiated groups to a level one-third that observed with tamoxifen administration to DEN-initiated rats. Both tamoxifen and toremifene increased the incidence of hypernephromas in previously DEN-initiated rats. While both tamoxifen and toremifene are effective promoting agents for DEN-initiated lesions, tamoxifen is more potent than toremifene in the induction of rat hepatocarcinogenesis.
 ...
PMID:Comparison of the effects of tamoxifen and toremifene on liver and kidney tumor promotion in female rats. 758 93

The effect of culture medium on glutathione (GSH) dependent detoxification defence system of primary cultured hepatocyte from either male or female rats was studied. Intracellular reduced (GSH) and oxidized glutathione (GSSG), and six GSH-related enzyme activities, including GSH peroxidase (GSH Px), GSH reductase (GSH Rd), cytosolic GSH S-transferase (cGST), microsomal GSH S-transferase (mGST), gamma-glutamyl transpeptidase (GTP), and gamma-glutamylcysteine synthetase (GCS), were investigated during a 6-day culture. Media free of fetal bovine serum (FBS) and with 2.5 or 10% FBS were used. Whatever the medium, there was an initial decrease of intracellular GSH and GSSG, a threefold increase of GSH at day 3 and fourfold increase of GSSG at day 4, later decreasing to their original level at day 6. The activities of all six GSH-related enzymes of male and female hepatocytes remained relatively stable during the first 72h, then gradually decreased to 50-80% of initial activities. With the exception of cGST, time-course profiles of other enzyme activities were not significantly different among various media. In both sexes, higher cGST activity was maintained for cells cultured in the presence of FBS. Results of immunoblotting analysis of cytosolic GST isozymes indicate that the placental form of GST (Yp) was markedly increased after plating and the extent of increase of Yp was higher in the presence of FBS. Despite the culture medium, the level of GST isoform Ya was maintained steadily for 6 days, however, Yb was maintained during the first 3 days and then decreased. In terms of the gender difference, GSH Px and GTP activities of hepatocytes from females were significantly greater than of males over the entire culture period. Results indicate that FBS seems not to be absolutely essential in maintaining GSH level and most of the GSH-related enzyme activities in rat hepatocytes. Furthermore, GSH levels and GSH-related enzyme activities of hepatocytes from female rats were similar to those from male rats.
 ...
PMID:Glutathione and glutathione-related enzyme activities of male and female rat hepatocytes under various culture conditions. 891 40

We report the isolation of three full-length cDNAs corresponding to the mRNAs of closely related glutathione S-transferase (GST) Pi genes, designated hGSTP1*A, hGSTP1*B, and hGSTP1*C, expressed in normal cells and malignant gliomas. The variant cDNAs result from A --> G and C --> T transitions at nucleotides +313 and +341, respectively. The transitions changed codon 104 from ATC (Ile) in hGSTP1*A to GTC (Val) in hGSTP1*B and hGSTP1*C and changed codon 113 from GCG (Ala) to GTG (Val) in hGSTP1*C. Both amino changes are in the electrophile-binding active site of the GST Pi peptide. Computer modeling of the deduced crystal structures of the encoded peptides showed significant deviations in the interatomic distances of critical electrophile-binding active site amino acids as a consequence of the amino acid changes. The encoded proteins expressed in Escherichia coli and purified by GSH affinity chromatography showed a 3-fold lower Km (CDNB) and a 3-4-fold higher Kcat/Km for the hGSTP1*A encoded protein than the proteins encoded by hGSTP1*B and hGSTP1*C. Analysis of 75 cases showed the relative frequency of hGSTP1*C to be 4-fold higher in malignant gliomas than in normal tissues. These data provide conclusive molecular evidence of allelopolymorphism of the human GST Pi gene locus, resulting in active, functionally different GST Pi proteins, and should facilitate studies of the role of this gene in xenobiotic metabolism, cancer, and other human diseases.
 ...
PMID:Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase Pi gene variants. Evidence for differential catalytic activity of the encoded proteins. 909 42

Exposure of the skin to sunlight results in an increase of the content of epidermal trans-urocanic acid, a key metabolite of L-histidine, and also in occurrence of the isomerization of trans-urocanic acid to the cis isomer. S-[2-Carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione (GS(CIE)), an adduct of urocanic acid and glutathione, is a presumed origin of a urinary compound S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-L-cysteine (Cys(CIE)). The formation of GS(CIE) is stimulated by exposing the skin to sunlight irradiation. In this study we investigated an enzymatic formation of GS(CIE) from glutathione and cis-urocanic acid by incubation with rat liver extract that contained glutathione S-transferase (GST) at high activity. The formation of GS(CIE) was suppressed significantly when a liver extract depleted of GST activity was used. Enzymatic degradation of GS(CIE) with gamma -glutamyl transpeptidase resulted in the formation of N-[S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-L-cysteinyl]glycine, a metabolic intermediate between the glutathione adduct and Cys(CIE). A hydrolyzed product of GS(CIE) by HCl was identical with the urinary Cys(CIE). Compounds were analyzed by high-voltage paper electrophoresis, capillary electrophoresis, and fast atom bombardment mass spectrometry. From these results, we suggest that GS(CIE) formed from cis-urocanic acid and glutathione is an origin of the urinary compound Cys(CIE) and that the formation reaction is catalyzed mostly by the action of GST.
 ...
PMID:Formation of S-[2-carboxy-1-(1H-imidazol-4-yl) ethyl]glutathione, a new metabolite of L-histidine, from cis-urocanic acid and glutathione by the action of glutathione S-transferase. 1451 47

The inhibitory activity of carpropamid on scytalone dehydratase (SDH) extracted from a carpropamid-resistant strain of Magnaporthe grisea (Hebert) Barr was dramatically reduced in comparison with that on SDH extracted from the sensitive strain. A single-point mutation (G to A) located at the upstream region (233 bp downstream from the ATG codon) resulting in a one-amino-acid substitution (valine [GTG] 75 to methionine [ATG]: V75M) was found in the resistant strain. To examine whether the V75M mutation is the primary reason for decreasing the sensitivity of SDH to carpropamid, the SDH cDNAs of both the sensitive and the resistant strain were cloned into a GST-fused protein expression vector-system. The recombinant SDHs of both strains exhibited the same sensitivities to carpropamid as those extracted from the mycelia of the respective strains. These data clearly revealed that the V75M mutation causes the low sensitivities of the SDHs of the carpropamid-resistant strains, and strongly suggests that the V75M mutation confers resistance of these strains to carpropamid.
 ...
PMID:Mechanism of resistance to carpropamid in Magnaporthe grisea. 1538 7

The eye colour mutant sepia (se1) is defective in PDA {6-acetyl-2-amino-3,7,8,9-tetrahydro-4H-pyrimido[4,5-b]-[1,4]diazepin-4-one or pyrimidodiazepine} synthase involved in the conversion of 6-PTP (2-amino-4-oxo-6-pyruvoyl-5,6,7,8-tetrahydropteridine; also known as 6-pyruvoyltetrahydropterin) into PDA, a key intermediate in drosopterin biosynthesis. However, the identity of the gene encoding this enzyme, as well as its molecular properties, have not yet been established. Here, we identify and characterize the gene encoding PDA synthase and show that it is the structural gene for sepia. Based on previously reported information [Wiederrecht, Paton and Brown (1984) J. Biol. Chem. 259, 2195-2200; Wiederrecht and Brown (1984) J. Biol. Chem. 259, 14121-14127; Andres (1945) Drosoph. Inf. Serv. 19, 45; Ingham, Pinchin, Howard and Ish-Horowicz (1985) Genetics 111, 463-486; Howard, Ingham and Rushlow (1988) Genes Dev. 2, 1037-1046], we isolated five candidate genes predicted to encode GSTs (glutathione S-transferases) from the presumed sepia locus (region 66D5 on chromosome 3L). All cloned and expressed candidates exhibited relatively high thiol transferase and dehydroascorbate reductase activities and low activity towards 1-chloro-2,4-dinitrobenzene, characteristic of Omega class GSTs, whereas only CG6781 catalysed the synthesis of PDA in vitro. The molecular mass of recombinant CG6781 was estimated to be 28 kDa by SDS/PAGE and 56 kDa by gel filtration, indicating that it is a homodimer under native conditions. Sequencing of the genomic region spanning CG6781 revealed that the se1 allele has a frameshift mutation from 'AAGAA' to 'GTG' at nt 190-194, and that this generates a premature stop codon. Expression of the CG6781 open reading frame in an se1 background rescued the eye colour defect as well as PDA synthase activity and drosopterins content. The extent of rescue was dependent on the dosage of transgenic CG6781. In conclusion, we have discovered a new catalytic activity for an Omega class GST and that CG6781 is the structural gene for sepia which encodes PDA synthase.
 ...
PMID:Identification and characteristics of the structural gene for the Drosophila eye colour mutant sepia, encoding PDA synthase, a member of the omega class glutathione S-transferases. 1671 27

Mice primed by feeding griseofulvin or diethyl 1,4-dihydro 1,4,6-trimethyl 3,5-pyridine decarboxylate for 5 months followed by drug withdrawal for 1 month (drug-primed mice) were given thioacetamide intraperitoneally, and the livers were subsequently studied at intervals up to 7 days. The hepatocellular proliferative response was measured by immunostaining for proliferative cell nuclear antigen. Necrosis was followed by measuring ALT. Mallory bodies were identified by immunoperoxidase stains for ubiquitin and cytokeratin. Preneoplastic foci were localized using immunofluorescence stain for glutathione S-transferase (GST mu) and histochemical stain for gamma glutamyl transpeptidase (GGT). The results showed that the preneoplastic foci selectively proliferated and expanded and formed nodules as indicated by quantitation of nuclei stained positive for proliferating cell nuclear antigen after thioacetamide treatment. Data support the hypothesis that the preneoplastic foci consisted of clones of hepatocytes which preferentially express GST mu, GGT and Mallory bodies. These preneoplastic cells selectively proliferate in response to the promoter effects of necrosis-induced liver cell regeneration ("chemical partial hepatectomy").
 ...
PMID:Preneoplastic liver cell foci expansion induced by thioacetamide toxicity in drug-primed mice. 1672 98

Chemoprevention is an important alternative approach to control cancer. Chemical substances with multiple inhibitory properties would be a welcome addition to the class of chemopreventive drugs. In this study, we investigated the antioxidant, anti-inflammatory, antimutagenic and cancer preventive activities of aqueous extract of a macrofungus Phellinus rimosus (Berk) Pilat. The extract exhibited superoxide anion (O2-), hydroxyl radical (*OH), nitric oxide (NO*) scavenging and lipid peroxidation inhibiting activities. The inhibitory concentrations required by the extract to scavenge 50% (IC50) of the superoxide anion, hydroxyl radical and nitric oxide generated were 126 +/- 5.1, 71 +/- 4.7 and 31 +/- 4.5 microg/ml respectively. The concentration required to inhibit 50% of Fe2+ induced lipid peroxidation in rat liver homogenate was 318 +/- 2.4 microg/ml. The extract showed significant (P<0.05) anti-inflammatory activity in a dose dependent manner. Extract (100 mg/kg body wt, p.o) inhibited 44.5, 45.4 and 47% carrageenen, dextran and formalin induced inflammations respectively. The antimutagenic activity was determined by the Ames' Salmonella mutagenecity assay using histidine mutant Salmonella typhimurium strains. The extract at concentration of 5 mg/plate showed antimutagenecity against benzo[a]pyrene (B[a]P) and 4-nitro-o-pheneylenediamine (NPDA) induced mutations of TA98 and TA100 respectively. Anticarcinogenic activity was evaluated using N-nitrosodiethylamine (NDEA) induced hepatocellular carcinoma (HCC) in rats. Serum gamma glutamyl transpeptidase (GGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) activities and lipid peroxidation level (MDA) were elevated significantly (P<0.05) in the NDEA alone treated group of animals. Treatment of the extract (25 and 50 mg/kg body wt, p.o.) prior to the NDEA administration decreased the serum GGT, GOT, GPT and ALP activities and MDA level in a dose dependent manner. The NDEA alone treated animals showed altered serum albumin/globulin ratio (A:G ratio), hyperfibrinogenaemia, increased hepatic glutathione S-transferase (GST) activity, glutathione-peroxidsae (GPx) activity and reduced glutathione (GSH) level compared to the extract plus NDEA treated group. The extract also inhibited in vitro aniline hydroxylase (AH) activity of rat liver induced by phenobarbitone in a dose dependent manner. The results, thus suggest the significant chemopreventive properties of the aqueous extract of the Phellinus rimosus against NDEA induced hepatocellular carcinoma by its antioxidant, anti-inflammatory and antimutagenic activities.
 ...
PMID:Chemopreventive activity of a macrofungus Phellinus rimosus against N-nitrosodiethylamine induced hepatocellular carcinoma in rat. 1702 71


1 2 3 4 Next >>