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pubmed-article:15734732pubmed:abstractTextThe antioxidant response element (ARE) and Nrf2 are known to regulate the expression and coordinated induction of genes encoding detoxifying enzymes including NAD(P)H:quinone oxidoreductase1 (NQO1) in response to antioxidants. In this report, we demonstrate that overexpression of the transcription factor Bach1 in Hep-G2 cells negatively regulated NQO1 gene expression and induction in response to antioxidant t-BHQ. Bandshift and supershift assays revealed that Bach1 binds to the ARE as a heterodimer with small Maf proteins but not as a homodimer or heterodimer with Nrf2. The transfection and ChIP assays revealed that Bach1 and Nrf2 competed with each other to regulate ARE-mediated gene expression. Heme, a negative regulator of Bach1 relieved the Bach1 repression of NQO1 gene expression in transfected cells. The transcription of Bach1 and Nrf2 did not change in response to t-BHQ. Immunofluorescence assays and Western blot analysis revealed that both Bach1 and Nrf2 localized in the cytoplasm and nucleus of the untreated cells. The treatment of cells with t-BHQ resulted in the nuclear accumulation of both Bach1 and Nrf2. Interestingly, the t-BHQ-induced nuclear accumulation of Bach1 was significantly delayed over that of Nrf2. These results led to the conclusion that a balance of Nrf2 versus Bach1 inside the nucleus influences up- or down-regulation of ARE-mediated gene expression. The results further suggest that antioxidant-induced delayed accumulation of Bach1 contributes to the down-regulation of ARE-regulated genes, presumably to reduce the antioxidant enzymes to normal levels.lld:pubmed
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pubmed-article:15734732pubmed:pagination16891-900lld:pubmed
pubmed-article:15734732pubmed:dateRevised2008-11-21lld:pubmed
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pubmed-article:15734732pubmed:year2005lld:pubmed
pubmed-article:15734732pubmed:articleTitleBach1 competes with Nrf2 leading to negative regulation of the antioxidant response element (ARE)-mediated NAD(P)H:quinone oxidoreductase 1 gene expression and induction in response to antioxidants.lld:pubmed
pubmed-article:15734732pubmed:affiliationDepartment of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA.lld:pubmed
pubmed-article:15734732pubmed:publicationTypeJournal Articlelld:pubmed
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