|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 33, 29561-29567, August 16, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Division of Pharmacology/Neurobiology, Biozentrum of the
University of Basel, Klingelbergstrasse 50-70,
CH-4056 Basel, Switzerland
Cytochromes P450 (CYP) constitute the major
enzymatic system for metabolism of xenobiotics. Here we demonstrate
that transcriptional activation of CYPs by the drug-sensing nuclear
receptors pregnane X receptor, constitutive androstane receptor,
and the chicken xenobiotic receptor (CXR) can be modulated by
endogenous cholesterol and bile acids. Bile acids induce the chicken
drug-activated CYP2H1 via CXR, whereas the hydroxylated metabolites of
bile acids and oxysterols inhibit drug induction. The
cholesterol-sensing liver X receptor competes with CXR, pregnane X
receptor, or constitutive androstane receptor for regulation of
drug-responsive enhancers from chicken CYP2H1, human CYP3A4, or human
CYP2B6, respectively. Thus, not only cholesterol 7 The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AF492497 and AF492498.
Cholesterol and Bile Acids Regulate Xenosensor Signaling in
Drug-mediated Induction of Cytochromes P450*
,
-hydroxylase
(CYP7A1), but also drug-inducible CYPs, are diametrically affected by
these receptors. Our findings reveal new insights into the increasingly
complex network of nuclear receptors regulating lipid homeostasis and
drug metabolism.
*
This work was supported by the Swiss National Science
Foundation.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: MyoContract, Pharmaceutical Research Ltd.,
Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
§
Present address: INSERM U128, CNRS, 1919 Route de Mende, F-34293
Montpellier Cedex 05, France.
¶
To whom correspondence should be addressed: Division of
Pharmacology/Neurobiology, Biozentrum of the University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel, Switzerland. Tel.:
41-61-267-22-20; Fax: 41-61-267-22-08; E-mail:
Urs-A.Meyer@unibas.ch.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  D. Masson, M. Qatanani, A. L. Sberna, R. Xiao, J. P. Pais de Barros, J. Grober, V. Deckert, A. Athias, P. Gambert, L. Lagrost, et al. Activation of the constitutive androstane receptor decreases HDL in wild-type and human apoA-I transgenic mice J. Lipid Res., August 1, 2008; 49(8): 1682 - 1691. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Morey, J. C. Ryan, M.-Y. Bottein Dechraoui, A. H. Rezvani, E. D. Levin, C. J. Gordon, J. S. Ramsdell, and F. M. Van Dolah Liver Genomic Responses to Ciguatoxin: Evidence for Activation of Phase I and Phase II Detoxification Pathways following an Acute Hypothermic Response in Mice Toxicol. Sci., June 1, 2008; 103(2): 298 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Roth, R. Looser, M. Kaufmann, S. M. Blattler, F. Rencurel, W. Huang, D. D. Moore, and U. A. Meyer Regulatory Cross-Talk between Drug Metabolism and Lipid Homeostasis: Constitutive Androstane Receptor and Pregnane X Receptor Increase Insig-1 Expression Mol. Pharmacol., April 1, 2008; 73(4): 1282 - 1289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li, O. Mezei, and N. F. Shay Human and Murine Hepatic Sterol-12-{alpha}-Hydroxylase and Other Xenobiotic Metabolism mRNA Are Upregulated by Soy Isoflavones J. Nutr., July 1, 2007; 137(7): 1705 - 1712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Talukdar and F. B. Hillgartner The mechanism mediating the activation of acetyl-coenzyme A carboxylase-{alpha} gene transcription by the liver X receptor agonist T0-901317 J. Lipid Res., November 1, 2006; 47(11): 2451 - 2461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Gnerre, G. U. Schuster, A. Roth, C. Handschin, L. Johansson, R. Looser, P. Parini, M. Podvinec, K. Robertsson, J.-A. Gustafsson, et al. LXR deficiency and cholesterol feeding affect the expression and phenobarbital-mediated induction of cytochromes P450 in mouse liver J. Lipid Res., August 1, 2005; 46(8): 1633 - 1642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Handschin and U. A. Meyer Induction of Drug Metabolism: The Role of Nuclear Receptors Pharmacol. Rev., December 1, 2003; 55(4): 649 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Ourlin, F. Lasserre, T. Pineau, J. M. Fabre, A. Sa-Cunha, P. Maurel, M.-J. Vilarem, and J. M. Pascussi The Small Heterodimer Partner Interacts with the Pregnane X Receptor and Represses Its Transcriptional Activity Mol. Endocrinol., September 1, 2003; 17(9): 1693 - 1703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Kocarek and N. A. Mercer-Haines Squalestatin 1-Inducible Expression of Rat CYP2B: Evidence That an Endogenous Isoprenoid Is an Activator of the Constitutive Androstane Receptor Mol. Pharmacol., November 1, 2002; 62(5): 1177 - 1186. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |