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Text
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URL Address
<a href="http://doi.org/10.1124/dmd.108.025155" target="_blank" rel="noreferrer noopener">http://doi.org/10.1124/dmd.108.025155</a>
Pages
469–478
Issue
3
Volume
37
Dublin Core
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Title
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Mechanism of vitamin D receptor inhibition of cholesterol 7alpha-hydroxylase gene transcription in human hepatocytes.
Publisher
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Drug metabolism and disposition: the biological fate of chemicals
Date
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2009
2009-03
Subject
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Base Sequence; Calcitriol/drug effects/genetics/*physiology; Cell Line; Cells; Cholesterol 7-alpha-Hydroxylase/*genetics; Cultured; DNA Primers; Electrophoretic Mobility Shift Assay; Gene Knockdown Techniques; Genetic/*physiology; Hepatocytes/*drug effects/enzymology; Humans; Immunoprecipitation; Lithocholic Acid/pharmacology; Messenger/genetics; Polymerase Chain Reaction; Receptors; RNA; Small Interfering; Transcription; Tumor; Two-Hybrid System Techniques
Creator
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Han Shuxin; Chiang John Y L
Description
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Lithocholic acid (LCA) is a potent endogenous vitamin D receptor (VDR) ligand. In cholestasis, LCA levels increase in the liver and intestine. The objective of this study is to test the hypothesis that VDR plays a role in inhibiting cholesterol 7alpha-hydroxylase (CYP7A1) gene expression and bile acid synthesis in human hepatocytes. Immunoblot analysis has detected VDR proteins in the nucleus of the human hepatoma cell line HepG2 and human primary hepatocytes. 1alpha, 25-Dihydroxy-vitamin D(3) or LCA acetate-activated VDR inhibited CYP7A1 mRNA expression and bile acid synthesis, whereas small interfering RNA to VDR completely abrogated VDR inhibition of CYP7A1 mRNA expression in HepG2 cells. Electrophoretic mobility shift assay and mutagenesis analyses have identified the negative VDR response elements that bind VDR/retinoid X receptor alpha in the human CYP7A1 promoter. Mammalian two-hybrid, coimmunoprecipitation, glutathione
Identifier
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<a href="http://doi.org/10.1124/dmd.108.025155" target="_blank" rel="noreferrer noopener">10.1124/dmd.108.025155</a>
Rights
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2009
Base Sequence
Calcitriol/drug effects/genetics/*physiology
Cell Line
Cells
Chiang John Y L
Cholesterol 7-alpha-Hydroxylase/*genetics
Cultured
Department of Integrative Medical Sciences
DNA Primers
Drug metabolism and disposition: the biological fate of chemicals
Electrophoretic Mobility Shift Assay
Gene Knockdown Techniques
Genetic/*physiology
Han Shuxin
Hepatocytes/*drug effects/enzymology
Humans
Immunoprecipitation
Lithocholic Acid/pharmacology
Messenger/genetics
NEOMED College of Medicine
Polymerase Chain Reaction
Receptors
RNA
Small Interfering
Transcription
Tumor
Two-Hybrid System Techniques