The Structure of Two Murine Class-Mu Glutathione Transferase Genes Coordinately Induced by Butylated Hydroxyanisole

Reinhart, John B.; Pearson, William R.

doi:10.1006/abbi.1993.1299

Cited by 21 publications

(28 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Western blotting was performed to monitor the levels of G S T ; Table 1 provides details of antibodies used [83-871. As expected from previous work, BHA markedly induced class Alpha and M u GST in the livers of male mice possessing intact NrfZ [83,84,88,89]. Figure 2 shows that, in comparison with the wildtype mouse, expression of the G S T A l and/or GSTA2, GSTA4, G S T M l and GSTM5 subunits is decreased substantially in male Nrf2 knock-out mice fed on a control R M l diet (supplied by SDS Ltd., Witham, Essex, U.K.).…”

Section: Identity Of Transcription Factors That Bind To the Aresupporting

confidence: 86%

The Nrf2 transcription factor contributes both to the basal expression of glutathione S-transferases in mouse liver and to their induction by the chemopreventive synthetic antioxidants, butylated hydroxyanisole and ethoxyquin

Hayes

Chanas

Henderson

et al. 2000

Biochemical Society Transactions

303

173

View full text Add to dashboard Cite

An overview is provided of the cancer chemoprevention actions of phenolic antioxidants and 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline (ethoxyquin). These agents principally appear to exert their beneficial effects through induction of phase II drug-metabolizing enzymes such as glutathione S-transferase (GST). The requirement for oxidative metabolism of the synthetic antioxidants to carbonyl-containing compounds, including quinones, in order that they can induce gene expression is discussed. Previous work has shown that the basic leucine zipper transcription factor Nrf2 is involved in induction of GST by the phenolic antioxidant butylated hydroxyanisole (BHA). Evidence is provided from a mouse possessing a targeted disruption of the Nrf2 gene that, in murine liver, the transcription factor regulates basal expression of several class Alpha and class Mu GST subunits, but not class Pi GST. In the Nrf2 knock-out mouse, hepatic induction of class Alpha and class Mu GST by BHA and the synthetic antioxidant ethoxyquin is similarly impaired, suggesting that these agents affect gene activation by a related mechanism. Significantly, residual induction of GST by antioxidants is apparent in the Nrf2 mutant mouse, indicating the existence of an alternative mechanism of gene activation.

show abstract

Section: Identity Of Transcription Factors That Bind To the Aresupporting

confidence: 86%

The Nrf2 transcription factor contributes both to the basal expression of glutathione S-transferases in mouse liver and to their induction by the chemopreventive synthetic antioxidants, butylated hydroxyanisole and ethoxyquin

Hayes

Chanas

Henderson

et al. 2000

Biochemical Society Transactions

303

173

View full text Add to dashboard Cite

show abstract

“…Mutations in the regions flanking the ARE core sequence blocked induction, demonstrating that the presence of the core sequence alone is insufficient to mediate a response. An ARE-like sequence from the GST-Mu promoter (30) was not inducible, despite the presence of a perfect ARE core sequence. A core-containing ARE-like sequence from the ␥-glutamylcysteine synthetase promoter (29) was also insufficient to mediate induction.…”

Section: Resultsmentioning

confidence: 95%

“…Recent findings have indicated that the novel 160-kDa factor ARE-binding protein 1 (ARE-BP-1) is likely to mediate the chemoprotective induction of detoxification genes through the ARE (28). ARE core sequences have been identified in the promoter regions of additional genes postulated to be members of the chemoprotective response system (29,30); however, when tested these ARE core sequences were not sufficient to mediate a response to chemoprotective compounds. This indicates that additional sequence information is necessary to define a functional ARE.…”

mentioning

confidence: 99%

Functional antioxidant responsive elements

Wasserman

Fahl

1997

Proc. Natl. Acad. Sci. U.S.A.

657

451

View full text Add to dashboard Cite

Exposure of human and rodent cells to a wide variety of chemoprotective compounds confers resistance against a broad set of carcinogens. For a subset of the chemoprotective compounds, protection is generated by an increase in the abundance of protective enzymes like glutathione S-transferases (GST). Antioxidant responsive elements (AREs) mediate the transcriptional induction of a battery of genes which comprise much of this chemoprotective response system. Past studies identified a necessary ARE ''core'' sequence of RTGACnnnGC, but this sequence alone is insufficient to mediate induction. In this study, the additional sequences necessary to define a sufficient, functional ARE are identified through systematic mutational analysis of the murine GST Ya ARE. Introduction of the newly identified necessary nucleotides into the regions flanking a nonresponsive, ARE-like, GST-Mu promoter sequence produced an inducible element. A screen of the GenBank database with the newly identified ARE consensus identified 16 genes which contained the functional ARE consensus sequence in their promoters. Included within this group was an ARE sequence from the murine ferritin-L promoter that mediated induction when tested. In an electrophoretic mobility-shift assay, the ferritin-L ARE was bound by ARE-binding protein 1, a protein previously identified as the likely mediator of the chemoprotective response. A three-level ARE classification system is presented to account for the distinct induction strengths observed in our mutagenesis studies. A model of the ARE as a composite regulatory site, where multiple transcription factors interact, is presented to account for the complex characteristics of AREmediated chemoprotective gene expression.

show abstract

“…The availability of the murine GSTM1 promoter sequence (Figure 2a; Reinhart and Pearson, 1993) enabled the PCR amplification of this region from mouse genomic DNA. Seven single-nucleotide differences were observed between the database entry and the sequence of our PCR product (Figure 2a), Three potential, albeit imperfect, Myb-binding sites (MBS) were identified in this sequence (Figure 2).…”

mentioning

confidence: 99%

“…Cotransfection of Myb or MybL3,4P with the empty pXPG vector, however, showed no Figure 2 Promoter sequence of the murine GSTM1 gene. (a) Sequence of the GSTM1 proximal promoter region (GenBank Accession Number L13448; Reinhart and Pearson, 1993). The exonic region is shown in bold, the transcription start site is at þ 1 and the translation initiation codon (ATG) is underlined.…”

mentioning

confidence: 99%

Regulation of the gene encoding glutathione S-transferase M1 (GSTM1) by the Myb oncoprotein

et al. 2003

View full text Add to dashboard Cite

The Structure of Two Murine Class-Mu Glutathione Transferase Genes Coordinately Induced by Butylated Hydroxyanisole

Cited by 21 publications

References 0 publications

The Nrf2 transcription factor contributes both to the basal expression of glutathione S-transferases in mouse liver and to their induction by the chemopreventive synthetic antioxidants, butylated hydroxyanisole and ethoxyquin

The Nrf2 transcription factor contributes both to the basal expression of glutathione S-transferases in mouse liver and to their induction by the chemopreventive synthetic antioxidants, butylated hydroxyanisole and ethoxyquin

Functional antioxidant responsive elements

Regulation of the gene encoding glutathione S-transferase M1 (GSTM1) by the Myb oncoprotein

Contact Info

Product

Resources

About