Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 433, Issue 2, Pages 387-396Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2004.08.030
Keywords
nuclear receptors; drug-induction; lipids; bile acids; cholesterol; CAR; PXR; LXR; FXR; cytochrome P450
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Cloning and characterization of the orphan nuclear receptors Constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2) led to major breakthroughs in Studying drug-mediated transcriptional induction of drug-metabolizing cytochromes P450 (CYPs). More recently, additional roles for CAR and PXR have been discovered. As examples, these xenosensors are involved in the homeostasis of cholesterol, bile acids, bilirubin, and other endogenous hydrophobic molecules in the liver: CAR and PXR thus form an intricate regulatory network with other members of the nuclear receptor superfamily, foremost the cholesterol-sensing liver X receptor (LXR, NR1H2/3) and the bile-acid-activated farnesoid X receptor (FXR, NR1H4). In this review, functional interactions between these nuclear receptors as well as the consequences on physiology and pathophysiology of the liver are discussed. (C) 2004 Elsevier Inc. All rights reserved.
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