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

• Published in: Biochemical and biophysical research communications Vol. 331; no. 4; pp. 1533 - 1541
• Main Authors: Sporstøl, Marita, Tapia, German, Malerød, Lene, Mousavi, Seyed Ali, Berg, Trond
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17-06-2005
• Subjects: ABCA1; Animals; ATP-Binding Cassette Transporters - metabolism; Base Sequence; CD36 Antigens; Cells, Cultured; Cholesterol; DNA Primers; Liver; Liver - drug effects; Liver - metabolism; Promoter Regions, Genetic; PXR; Rats; Rats, Wistar; Receptors, Cytoplasmic and Nuclear - agonists; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Receptors, Scavenger; Receptors, Steroid - agonists; Scavenger Receptors, Class B; SR-BI; ABCA1; SR-BI; PXR; Liver; Cholesterol
• ISSN: 0006-291X; 1090-2104
• 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 16α-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).