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rdf:type |
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lifeskim:mentions |
umls-concept:C0003402,
umls-concept:C0017262,
umls-concept:C0127400,
umls-concept:C0205160,
umls-concept:C0205263,
umls-concept:C0600508,
umls-concept:C0719453,
umls-concept:C0851285,
umls-concept:C0871261,
umls-concept:C1136197,
umls-concept:C1412729,
umls-concept:C1417701,
umls-concept:C1426958,
umls-concept:C1522538,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2911692
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pubmed:issue |
17
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pubmed:dateCreated |
2005-4-25
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pubmed:abstractText |
The 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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/BACH1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Basic-Leucine Zipper Transcription...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fanconi Anemia Complementation...,
http://linkedlifedata.com/resource/pubmed/chemical/Heme,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/MAF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/NAD(P)H Dehydrogenase (Quinone),
http://linkedlifedata.com/resource/pubmed/chemical/NF-E2-Related Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/NFE2L2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/NQO1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-maf,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
29
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
16891-900
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15734732-Antioxidants,
pubmed-meshheading:15734732-Base Sequence,
pubmed-meshheading:15734732-Basic-Leucine Zipper Transcription Factors,
pubmed-meshheading:15734732-Binding, Competitive,
pubmed-meshheading:15734732-Blotting, Northern,
pubmed-meshheading:15734732-Blotting, Western,
pubmed-meshheading:15734732-Cell Line,
pubmed-meshheading:15734732-Cell Line, Tumor,
pubmed-meshheading:15734732-Cell Nucleus,
pubmed-meshheading:15734732-Chromatin Immunoprecipitation,
pubmed-meshheading:15734732-Cytoplasm,
pubmed-meshheading:15734732-DNA-Binding Proteins,
pubmed-meshheading:15734732-Dimerization,
pubmed-meshheading:15734732-Down-Regulation,
pubmed-meshheading:15734732-Fanconi Anemia Complementation Group Proteins,
pubmed-meshheading:15734732-Gene Expression Regulation,
pubmed-meshheading:15734732-Genes, Reporter,
pubmed-meshheading:15734732-Heme,
pubmed-meshheading:15734732-Humans,
pubmed-meshheading:15734732-Kinetics,
pubmed-meshheading:15734732-Luciferases,
pubmed-meshheading:15734732-Microscopy, Fluorescence,
pubmed-meshheading:15734732-Molecular Sequence Data,
pubmed-meshheading:15734732-NAD(P)H Dehydrogenase (Quinone),
pubmed-meshheading:15734732-NF-E2-Related Factor 2,
pubmed-meshheading:15734732-Plasmids,
pubmed-meshheading:15734732-Promoter Regions, Genetic,
pubmed-meshheading:15734732-Protein Binding,
pubmed-meshheading:15734732-Protein Biosynthesis,
pubmed-meshheading:15734732-Proto-Oncogene Proteins,
pubmed-meshheading:15734732-Proto-Oncogene Proteins c-maf,
pubmed-meshheading:15734732-RNA, Messenger,
pubmed-meshheading:15734732-Response Elements,
pubmed-meshheading:15734732-Subcellular Fractions,
pubmed-meshheading:15734732-Time Factors,
pubmed-meshheading:15734732-Trans-Activators,
pubmed-meshheading:15734732-Transcription, Genetic,
pubmed-meshheading:15734732-Transcription Factors,
pubmed-meshheading:15734732-Transfection,
pubmed-meshheading:15734732-Up-Regulation
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pubmed:year |
2005
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pubmed:articleTitle |
Bach1 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.
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pubmed:affiliation |
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA.
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pubmed:publicationType |
Journal Article
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