rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
1999-3-30
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pubmed:databankReference |
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pubmed:abstractText |
The endogenous CYP2B6 gene becomes phenobarbital (PB) inducible in androstenol-treated HepG2 cells either transiently or stably transfected with a nuclear receptor CAR expression vector. The PB induction mediated by CAR is regulated by a conserved 51-base pair element called PB-responsive enhancer module (PBREM) that has now been located between -1733 and -1683 bp in the gene's 5'-flanking region. An in vitro translated CAR acting as a retinoid X receptor alpha heterodimer binds directly to the two nuclear receptor sites NR1 and NR2 within PBREM. In a stably transfected HepG2 cell line, both PBREM and NR1 are activated by PB and PB-type compounds such as chlorinated pesticides, polychlorinated biphenyls and chlorpromazine. In addition to PBREM, CAR also transactivates the steroid/rifampicin-response element of the human CYP3A4 gene in HepG2 cells. Thus, activation of the repressed nuclear receptor CAR appears to be a versatile mediator that regulates PB induction of the CYP2B and other genes.
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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/Aryl Hydrocarbon Hydroxylases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases, N-Demethylating,
http://linkedlifedata.com/resource/pubmed/chemical/Phenobarbital,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/S-mephenytoin N-demethylase,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/constitutive androstane receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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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 |
5
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pubmed:volume |
274
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6043-6
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10037683-Aryl Hydrocarbon Hydroxylases,
pubmed-meshheading:10037683-Base Sequence,
pubmed-meshheading:10037683-Cytochrome P-450 Enzyme System,
pubmed-meshheading:10037683-Excitatory Amino Acid Antagonists,
pubmed-meshheading:10037683-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:10037683-Humans,
pubmed-meshheading:10037683-Molecular Sequence Data,
pubmed-meshheading:10037683-Oxidoreductases, N-Demethylating,
pubmed-meshheading:10037683-Phenobarbital,
pubmed-meshheading:10037683-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:10037683-Signal Transduction,
pubmed-meshheading:10037683-Trans-Activators,
pubmed-meshheading:10037683-Transcription Factors,
pubmed-meshheading:10037683-Transfection,
pubmed-meshheading:10037683-Tumor Cells, Cultured
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pubmed:year |
1999
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pubmed:articleTitle |
The repressed nuclear receptor CAR responds to phenobarbital in activating the human CYP2B6 gene.
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pubmed:affiliation |
Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
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pubmed:publicationType |
Journal Article
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