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LXR deficiency and cholesterol feeding affect the expression and phenobarbital-mediated induction of cytochromes P450 in mouse liver

Gnerre, C. and Schuster, G. U. and Roth, A. and Handschin, C. and Johansson, L. and Looser, R. and Parini, P. and Podvinec, M. and Robertsson, K. and Gustafsson, J. -A. and Meyer, U. A.. (2005) LXR deficiency and cholesterol feeding affect the expression and phenobarbital-mediated induction of cytochromes P450 in mouse liver. Journal of Lipid Research, 46 (8). pp. 1633-1642.

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Official URL: http://edoc.unibas.ch/dok/A5258727

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Abstract

Metabolic transformation by the superfamily of cytochromes P450 (CYPs) plays an important role in the detoxification of xenobiotics such as drugs, environmental pollutants, and food additives. Endogenous substrates of CYPs include fatty acids, sterols, steroids, and bile acids. Induction of CYPs via transcriptional activation by substrates and other xenobiotics is an important adaptive mechanism that increases the organism's defense capability against toxicity. Numerous in vivo and in vitro data have highlighted the concept that the molecular mechanism of hepatic drug induction is linked to endogenous regulatory pathways. In particular, in vitro data suggest that oxysterols via the liver X receptor (LXR) inhibit phenobarbital (PB)-mediated induction of CYPs. To study the link between LXR, cholesterol homeostasis, and drug induction in vivo, we designed experiments in wild-type, LXRalpha-, LXRbeta-, and LXRalpha/beta-deficient mice. Our data expose differential regulatory patterns for Cyp2b10 and Cyp3a11 dependent on the expression of LXR isoforms and on challenge of cholesterol homeostasis by excess dietary cholesterol. Our results suggest that, in the mouse, liver cholesterol status significantly alters the pattern of expression of Cyp3a11, whereas the absence of LXR leads to an increase in PB-mediated activation of Cyp2b10.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Associated Research Groups > Pharmakologie (Handschin)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Growth & Development (Handschin)
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Research IT (Podvinec)
UniBasel Contributors:Handschin, Christoph and Podvinec, Michael
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0022-2275
e-ISSN:1539-7262
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:21 Nov 2017 13:10
Deposited On:22 Mar 2012 13:20

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