Pregnane X receptor-agonists down-regulate hepatic ATP-binding cassette transporter A1 and scavenger receptor class B type I

Biochem Biophys Res Commun. 2005 Jun 17;331(4):1533-41. doi: 10.1016/j.bbrc.2005.04.071.


Pregnane X receptor (PXR) is the molecular target for a wide variety of endogenous and xenobiotic compounds. It regulates the expression of genes central to the detoxification (cytochrome P-450 enzymes) and excretion (xenobiotic transporters) of potentially harmful compounds. The aim of the present investigation was to determine the role of PXR in regulation of high-density lipoprotein (HDL) cholesterol metabolism by studying its impact on ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI) expression in hepatocytes. ABCA1 and SR-BI are major factors in the exchange of cholesterol between cells and HDL. Expression analyses were performed using Western blotting and quantitative real time RT-PCR. Luciferase reporter gene assays were used to measure promoter activities. Total cholesterol was measured enzymatically after lipid extraction (Folch's method). The expression of ABCA1 and SR-BI was inhibited by the PXR activators rifampicin and lithocholic acid (LCA) in HepG2 cells and pregnenolone 16alpha-carbonitrile (PCN) in primary rat hepatocytes. Thus, PXR appears to be a regulator of hepatic cholesterol transport by inhibiting genes central to cholesterol uptake (SR-BI) and efflux (ABCA1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Base Sequence
  • CD36 Antigens
  • Cells, Cultured
  • DNA Primers
  • Liver / drug effects*
  • Liver / metabolism
  • Pregnane X Receptor
  • Promoter Regions, Genetic
  • Rats
  • Rats, Wistar
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Receptors, Scavenger
  • Receptors, Steroid / agonists*
  • Scavenger Receptors, Class B


  • ATP-Binding Cassette Transporters
  • CD36 Antigens
  • DNA Primers
  • Pregnane X Receptor
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Immunologic
  • Receptors, Scavenger
  • Receptors, Steroid
  • Scarb1 protein, rat
  • Scavenger Receptors, Class B