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Open Access Green as soon as Postprint is submitted to ZB.
Species-specific mechanisms for cholesterol 7α -hydroxylase (CYP7A1) regulation by drugs and bile acids.
Arch. Biochem. Biophys. 434, 75-85 (2005)
The gene encoding cholesterol 7alpha-hydroxylase (CYP7A1) is tightly regulated in order to control intrahepatic cholesterol and bile acid levels. Ligands of the xenobiotic-sensing pregnane X receptor inhibit CYP7A1 expression. To retrace the evolution of the molecular mechanisms underlying CYP7A1 inhibition, we used a chicken hepatoma cell system that retains the ability to be induced by phenobarbital and other drugs. Whereas bile acids regulate CYP7A1 via small heterodimer partner and liver receptor homolog-1, mRNA expression of these nuclear receptors is unchanged by xenobiotics. Instead, drugs repress chicken hepatic nuclear factor 4alpha (HNF4alpha) transcript levels concomitant with a reduction in CYP7A1 expression. Importantly, no reduction of HNF4alpha levels is found in mouse liver in vivo and in human primary hepatocyte cultures, respectively. Thus, besides the importance of HNF4alpha in CYP7A1 regulation in all species, birds and mammals use different signaling pathways to adjust CYP7A1 levels after exposure to xenobiotics.
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Publication type
Article: Journal article
Document type
Scientific Article
ISSN (print) / ISBN
0003-9861
e-ISSN
1096-0384
Quellenangaben
Volume: 434,
Issue: 1,
Pages: 75-85
Publisher
Elsevier
Reviewing status
Peer reviewed
Institute(s)
Helmholtz Pioneer Campus (HPC)