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)

We have constructed a retroviral bicistronic vector, MFG/GID, that transduces the expression of both the A3 isoform of the rat glutathione S-transferase (GST A3), and the tyr-22 variant of the human dihydrofolate reductase (DHFR(L22Y)). Transduction of murine 3T3 fibroblasts with this vector increased their in vitro resistance to chlorambucil (1.8-fold) and trimetrexate (TMTX) (748-fold). TMTX selection of a mixed population of 20% GID-transduced NIH 3T3 cells and 80% control cells resulted in a marked increase in the GST peroxidase activity associated with the GST A3 isoform (17.7-fold). MFG/GID-transduced primary clonogenic murine hematopoietic progenitor cells were likewise more resistant to TMTX and chlorambucil than control beta-gal-transduced cells. Selecting GID-transduced hematopoietic cells with a combination of TMTX and a nucleoside transport inhibitor resulted in a marked increase in resistance upon re-exposure to TMTX (99% survival). Similarly, GID-transduced hematopoietic cells selected with TMTX were more resistant to chlorambucil, with 40% survival at a drug concentration that killed practically all control cells. These results suggest that antifolate-mediated selection of MFG/GID-transduced hematopoietic cells could be used as a mean to enrich the population of transduced cells prior to or following transplantation, thus potentially conferring in vivo chemoprotection to nitrogen mustards and antifolates.
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PMID:Increased resistance to nitrogen mustards and antifolates following in vitro selection of murine fibroblasts and primary hematopoietic cells transduced with a bicistronic retroviral vector expressing the rat glutathione S-transferase A3 and a mutant dihydrofolate reductase. 1287 45

Glutathione S-transferases constitute a superfamily of enzymes that catalyse the inactivating conjugation of endogenous and environmental substrates involved in the pathogenesis of hepatocellular carcinoma (HCC) and glutathione. Genes encoding either glutathione S-transferase Mu-1 or Theta-1 (GSTM1 and GSTT1, respectively) isoforms are polymorphic. Homozygotes for the mutated inactive alleles of each gene are devoid of any specific enzymatic activity (null genotypes). Our aim was to investigate whether individuals with null GST genotypes have a higher risk of developing HCC. A total of 184 Caucasian Spanish patients with a diagnosis of HCC and 329 healthy controls of the same ethnic origin were included. Polymorphisms in GSTM1 and GSTT1 genes were identified through multiplex polymerase chain reactions, and the dihydrofolate reductase (DHFR) gene was used as internal control. No differences were found between the frequencies of GSTM1 (47.8% versus 45.3%) and GSTT1 (28.8% versus 23.1%) null genotypes in cases and controls, respectively, nor in the proportion of carriers of two, one or no active genotypes. Gender, age at diagnosis, tobacco use, chronic infection with hepatitis B or C virus and alcohol abuse did not influence these results. In conclusion, polymorphisms in GSTM1 and GSTT1 genes are not related to the incidence of HCC in a high-risk Spanish population.
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PMID:Glutathione S-transferase M1 and T1 genetic polymorphisms are not related to the risk of hepatocellular carcinoma: a study in the Spanish population. 1631 88

This study examined the toxic potential of a primary-treated municipal effluent, before and after ozonation, in freshwater mussels. Animals were exposed to various concentrations (0, 1, 3, 10 and 20% v/v) of a primary-treated effluent and also after a treatment with ozone at 10 mg/L in continuous flow-through mode for seven weeks. A suite of biomarkers was used to assess the potential toxic effects of various contaminants typically present in municipal wastewaters: heavy metal metabolism (metallothioneins and labile zinc), cytochrome P4501A1 and 3A4, glutathione S-transferase activities (biotransformation of organic compounds), lipid peroxidation and xanthine oxidoreductase (oxygen radical scavenging), DNA damage, mitochondrial electron transport activity at various temperatures and gonad lipid levels (cellular energy allocation) and aspartate transcarbamoylase and dihydrofolate reductase (gonad activity). On the one hand, some biomarkers, including metallothioneins, labile zinc, glutathione S-transferase, cytochrome P4503A4 activity, dehydrofolate reductase and aspartate transcarbamoylase, were readily decreased. In contrast, these biomarkers, cytochrome P4501A1, gill lipid peroxidation, DNA strand breaks in gills and digestive gland, mitochondrial electron transport at high and low temperatures (temperature-dependent activity) and total gonad lipids, were readily increased. In general, ozone treatment reduced adverse effects by either decreasing the intensity of the toxic responses or increasing the threshold concentration. For gill lipid peroxidation, however, intensity was greater at a higher threshold concentration. Ozone treatment eliminated the temperature sensitivity of the mitochondrial electron transport system, indicating a loss of interaction between temperature and urban pollution in terms of energy expenditure in mussels. Ozone treatment could significantly decrease either the toxic potency or intensity of urban pollutants at the expense of increased oxidative stress in gills of freshwater mussels.
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PMID:Toxicological effects of primary-treated urban wastewaters, before and after ozone treatment, on freshwater mussels (Elliptio complanata). 1738 41

The complete folate biosynthesis pathway exists in the genome of a rickettsial endosymbiont of Ixodes pacificus, Rickettsia monacensis strain Humboldt (formerly known as Rickettsia species phylotype G021). Recently, our lab demonstrated that the folA gene of strain Humboldt, the final gene in the folate biosynthesis pathway, encodes a functional dihydrofolate reductase enzyme. In this study, we report R. monacensis strain Humboldt has a functional GTP cyclohydrolase I (GCH1), an enzyme required for the hydrolysis of GTP to form 7,8-dihydroneopterin triphosphate in the folate biosynthesis pathway. The GCH1 gene of R. monacensis, folE, share homology with the folE gene of R. monacensis strain IrR/Munich, with a nucleotide sequence identity of 99%. Amino acid alignment and comparative protein structure modeling have shown that the FolE protein of R. monacensis has a conserved core subunit of GCH1 from the T-fold structural superfamily. All amino acid residues, including conserved GTP binding sites and zinc binding sites, are preserved in the FolE protein of R. monacensis. A recombinant GST-FolE protein from R. monacensis was overexpressed in Escherichia coli, purified by affinity chromatography, and assayed for enzyme activity in vitro. The in vitro enzymatic assay described in this study accorded the recombinant GCH1 enzyme of R. monacensis with a specific activity of 0.81 U/mg. Our data suggest folate genes of R. monacensis strain Humboldt have the potential to produce biochemically active enzymes for de novo folate synthesis, addressing the physioecological underpinnings behind tick-Rickettsia symbioses.
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PMID:GTP cyclohydrolase I activity from Rickettsia monacensis strain Humboldt, a rickettsial endosymbiont of Ixodes pacificus. 3241 95


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