Oxysterol-activated LXRalpha/RXR induces hSR-BI-promoter activity in hepatoma cells and preadipocytes.
SR-BI mediates exchange of cholesterol between HDL and cells, and is a crucial factor in the transport of excessive cellular cholesterol from extrahepatic tissues to the liver ("reverse cholesterol transport") and, therefore, also for cholesterol homeostasis. Hepatic SR-BI mediates transfer of HDL-cholesterol to the hepatocytes where cholesterol may be metabolised to bile acids. LXR and SREBP are key factors in the regulation of cholesterol metabolism. The purpose of the present study was to determine whether these transcription factors are involved in the regulation of SR-BI. Here we show that LXRalpha/RXR and LXRbeta/RXR induce SR-BI transcription in human and murine hepatoma cell lines, and in 3T3-L1 preadipocytes independently of SREBP-1. The LXR/RXR response was mapped within -1,200 to -937 of the promoter region. Gel mobility shift analysis confirmed that the putative LXR response element bound LXRalpha/RXR and LXRbeta/RXR heterodimers.
Malerød
Lene
L
Divison of Molecular Cell Biology, Institute of Biology, University of Oslo, P.O. Box 1050, Blindern, N-0316 Oslo, Norway.
Juvet
Lene K
LK
Hanssen-Bauer
Audun
A
Eskild
Winnie
W
Berg
Trond
T
D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology; D018955:CD36 Antigens / Q000096:biosynthesis / Q000235:genetics*; D019556:COS Cells; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology; D005822:Genetic Vectors; D006888:Hydroxycholesterols / Q000494:pharmacology*; D000071518:Liver X Receptors; D008565:Membrane Proteins; D051379:Mice; D057093:Orphan Nuclear Receptors; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D051116:Receptors, Scavenger; D020218:Response Elements; D047488:Retinoid X Receptors; D012190:Retroviridae / Q000235:genetics; D051122:Scavenger Receptors, Class B; D017384:Sequence Deletion; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D022762:CCAAT-Enhancer-Binding Proteins; D018955:CD36 Antigens; D004268:DNA-Binding Proteins; D006888:Hydroxycholesterols; D000071518:Liver X Receptors; D008565:Membrane Proteins; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D018168:Receptors, Retinoic Acid; D051116:Receptors, Scavenger; D047488:Retinoid X Receptors; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; C003585:22-hydroxycholesterol