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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
14
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pubmed:dateCreated |
2002-7-23
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pubmed:abstractText |
The 5' flanking region of the bile salt export pump (Bsep) gene was systematically analysed to provide the basis for understanding the mechanisms which regulate Bsep transcription. In addition substrates and drugs were investigated for their ability to alter Bsep promoter activity. Bsep promoter function was restricted to hepatocyte derived HepG2 cells. The 5' deletional analysis revealed a biphasic shape of reporter gene activities, indicating a suppressive element between nucleotides -800 and -512. Two consensus sites for the farnesoid X receptor (FXR) were located at nucleotides -473 and -64. The latter was characterized as functionally active in bile acid-mediated feed-back regulation of Bsep transcription. Bsep promoter activity was reduced by rifampin and beta-estradiol. The anti-estrogen tamoxifen stimulated promoter activity. Dexamethasone, hydrocortisone and phenobarbital had no effect on Bsep promoter activity. In conclusion, the data suggest that transcriptional regulation of the Bsep gene can be modulated by a number of endogenous compounds and xenobiotics. FXR was a major regulatory factor, mediating bile acid feed-back stimulation of Bsep transcription.
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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/ABCB11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Abcb11 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Bile Acids and Salts,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrocortisone,
http://linkedlifedata.com/resource/pubmed/chemical/Phenobarbital,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Rifampin,
http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Xenobiotics,
http://linkedlifedata.com/resource/pubmed/chemical/farnesoid X-activated receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0014-2956
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
269
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3495-503
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12135489-ATP-Binding Cassette Transporters,
pubmed-meshheading:12135489-Animals,
pubmed-meshheading:12135489-Base Sequence,
pubmed-meshheading:12135489-Bile Acids and Salts,
pubmed-meshheading:12135489-Binding Sites,
pubmed-meshheading:12135489-DNA-Binding Proteins,
pubmed-meshheading:12135489-Dexamethasone,
pubmed-meshheading:12135489-Feedback,
pubmed-meshheading:12135489-Gene Expression Regulation,
pubmed-meshheading:12135489-Genes,
pubmed-meshheading:12135489-Genes, Reporter,
pubmed-meshheading:12135489-Hepatoblastoma,
pubmed-meshheading:12135489-Hepatocytes,
pubmed-meshheading:12135489-Humans,
pubmed-meshheading:12135489-Hydrocortisone,
pubmed-meshheading:12135489-Liver Neoplasms,
pubmed-meshheading:12135489-Molecular Sequence Data,
pubmed-meshheading:12135489-Phenobarbital,
pubmed-meshheading:12135489-Promoter Regions, Genetic,
pubmed-meshheading:12135489-Rats,
pubmed-meshheading:12135489-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:12135489-Recombinant Fusion Proteins,
pubmed-meshheading:12135489-Rifampin,
pubmed-meshheading:12135489-Tamoxifen,
pubmed-meshheading:12135489-Transcription, Genetic,
pubmed-meshheading:12135489-Transcription Factors,
pubmed-meshheading:12135489-Transfection,
pubmed-meshheading:12135489-Tumor Cells, Cultured,
pubmed-meshheading:12135489-Xenobiotics
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pubmed:year |
2002
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pubmed:articleTitle |
Functional analysis of the rat bile salt export pump gene promoter.
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pubmed:affiliation |
Institute of Clinical Pharmacology, Charité University Medical Center, Humboldt University, Berlin, Germany. thomas.gerloff@gmx.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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