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)

Three murine liver glutathione transferase (GT, EC 2.5.1.18) have been cloned and sequenced. Two of the cDNA clones, pGT875 and pGT55, encode the murine class-mu GT isoenzymes, GT8.7 and GT9.3, respectively. These two cDNA clones share 85% DNA sequence identity with one another, and the GT8.7 sub-unit encoded by pGT875 shares 92% protein sequence identity with the class-mu rat-3 (Yb1) GT subunit. The third cDNA clone, pGT41, encodes a class-alpha GT subunit that shares 96% protein sequence identity with a mouse Ya gene, 95% identity with a rat-1 (Ya) GT subunit, and 70% identity with the rat-2 (Yc) subunit. These cDNA clones and an oligonucleotide derived from the sequence of a rat class-pi cDNA clone were used to measure the induction of the mu, alpha, and pi classes of GT mRNA in different tissues of mice that were fed the dietary antioxidant 2(3)-tert-butyl hydroxyanisole (BHA). These tissues included liver, intestinal mucosa, kidney, lung, spleen, and brain. Class-mu GT mRNAs that hybridize with pGT875 are most abundant in liver and intestinal mucosa but are also found in kidney and lung, and at low levels in brain and spleen. Class-alpha GT mRNAs are most abundant in BHA-induced and uninduced intestinal mucosa, kidney, and induced liver, and were not found in spleen and brain. Class-mu and -alpha GT mRNA levels increased 15- and 50-fold, respectively, in the liver and 15- and 100-fold in intestinal mucosa in response to BHA induction. BHA increases class-mu mRNAs less than 5-fold in the kidney and lung. Class-pi mRNAs were found in all the tissues examined but were much less responsive to BHA induction. The expression of two cytochrome P-450 mRNAs increased 3-5-fold in liver and intestine after BHA induction. Oligonucleotides from divergent portions of the pGT875 and pGT55 cDNA clones have been used to examine the expression of specific mRNAs from individual class-mu GT genes; these experiments suggest that the GT mRNAs expressed in BHA-induced tissues are also expressed in the uninduced tissue. Measurements of transcription rates in isolated nuclei showed that increased GT mRNA levels are due to increased rates of transcription.
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PMID:Tissue-specific induction of murine glutathione transferase mRNAs by butylated hydroxyanisole. 341 59

Levels of mRNAs encoding class-alpha glutathione transferases, class-mu glutathione transferases, quinone reductase, and cytochrome P450 1A were measured after xenobiotic induction in murine tissues and in the Hepa1c1c7 murine hepatoma cell line. RNA levels in liver and intestinal mucosa were determined after induction with phenobarbital, butylated hydroxyanisole, beta-naphthoflavone, isosafrole, or combinations of these compounds. The tissue culture cells were presented with combinations of butylated hydroxyanisole, tert-butyl-hydroquinone, and beta-naphthoflavone. In murine liver and intestinal mucosa, the greatest induction (5-15-fold) of glutathione transferases and quinone reductase was seen with butylated hydroxyanisole. Administration of phenobarbital or beta-naphthoflavone has only a modest effect (2-3-fold). In contrast, cytochrome P450 1A mRNA levels increase only slightly after BHA induction but are induced dramatically by beta-naphthoflavone. The pattern of induction is different in Hepa1c1c7 cells; there the greatest induction of all mRNAs occurred with beta-naphthoflavone. Administration of antioxidants with other xenobiotics increases mRNA levels only slightly over the levels obtained with BHA in murine tissues, or with beta-naphthoflavone in Hepa1c1c7 cells. mGSTM1 (GT8.7, Yb1), the most abundant glutathione transferase mRNA in murine liver, is also the most abundant glutathione transferase mRNA in both normal and induced Hepa1c1c7 cells. Our results suggest that BHA induction in murine liver and intestinal mucosa of class-mu and class-alpha glutathione transferases may involve regulatory elements and mediators that function poorly in Hepa1c1c7 cells.
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PMID:Differences in induction by xenobiotics in murine tissues and the Hepa1c1c7 cell line of mRNAs encoding glutathione transferase, quinone reductase, and CYP1A P450s. 822 Apr 36

We report the sequences of two coordinately induced murine glutathione transferase genes, mGSTM1 (GT8.7, Yb1) and mGSTM3 (GT9.3). Genomic clones covering the entire mGSTM1 gene were isolated; comparison of the mGSTM1 gene with genomic sequences from rat class-mu glutathione transferase genes suggests that the mGSTM1 gene is orthologous to the rGSTM1 (rat3, Yb1) gene. The start of mGSTM1 mRNA transcription was mapped by primer extension and RNase protection to 37 nucleotides upstream from the initiation codon. The 160 nucleotides 5'-proximal to the start of transcription match exactly the 5'-end of the class-mu glutathione transferase cDNA clone pmGT10. An mRNA transcript was found approximately 2.0 kb upstream from the start of mGSTM1 transcription; its sequence does not show significant similarity to other sequences in the DNA or protein sequence databases. The mGSTM1 gene contains a TATAAA sequence at -31 nucleotides upstream from the start of transcription, but no exact match to the antioxidant response element (RGTGACNNNGC), the xenobiotic response element (TNGCGTG), or the AP-1 consensus (TGASTMA) is found in the 5'-flanking region, although near matches are found in the 5'-flanking region, in intron 1, and in other parts of the gene. A genomic clone containing the first five exons of the mGSTM3 gene was also isolated. The mGSTM3 gene contains several repetitive elements--two upstream from the start of transcription and one within intron 2--that disrupt its similarity with the mGSTM1 gene. The 5'-flanking sequence of the mGSTM3 gene does not contain a TATAAA sequence or any exact matches to ARE or XRE consensus sequences, although an Sp1 binding site is found at -66. mGSTM3 and mGSTM1 diverge substantially outside their exons and share less than 60% sequence identity in the 5'-flanking region. Thus, it is likely that the mGSTM1-mGSTM3 gene duplication predates the rat-mouse divergence. The strongest region of conservation between the mGSTM1 gene and the mGSTM3 gene occurs in exon 3, intron 3, and exon 4; this region also shares strong similarity with the rGSTM1 (rat3, Yb1) and rGSTM2 (rat4, Yb2) genes.
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PMID:The structure of two murine class-mu glutathione transferase genes coordinately induced by butylated hydroxyanisole. 851 23