Hepatic scavenger receptor class B, type I is stimulated by peroxisome proliferator-activated receptor gamma and hepatocyte nuclear factor 4alpha.
Excessive cellular cholesterol is transported to the liver by a pathway called 'reverse cholesterol transport.' Scavenger receptor class B, type I (SR-BI) mediates cholesterol uptake in the liver. Polyunsaturated fatty acids, known to activate peroxisome proliferator-activated receptor (PPAR), have been reported to increase hepatic cholesterol uptake. We found in the present study that PPARgamma induces expression of SR-BI in rat hepatocytes, liver endothelial cells, and Kupffer cells. In contrast, PPARalpha increased SR-BI levels only in hepatocytes and liver endothelial cells. PPARgamma/RXR binds to a response element between -459 and -472 bp in the human SR-BI promoter. Furthermore, hepatocyte nuclear factor 4alpha (HNF4alpha) was found to enhance PPARgamma-mediated SR-BI transcription. Thiazolidinedione (TZD)-activated PPARgamma/RXR increased hepatic SR-BI levels, which may lead to increased hepatic cholesterol uptake and less accumulation of lipids in peripheral tissues. The present results are in agreement with previous reports, indicating that specific PPARgamma-agonists (such as TZDs) protect against atherosclerosis.
Malerød
Lene
L
Division of Molecular Cell Biology, Institute of Biology, University of Oslo, P.O. Box 1050, Blindern, Oslo 0316, Norway.
Sporstøl
Marita
M
Juvet
Lene K
LK
Mousavi
Ali
A
Gjøen
Tor
T
Berg
Trond
T
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001665:Binding Sites; D018955:CD36 Antigens / Q000096:biosynthesis / Q000235:genetics*; D019556:COS Cells; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D051116:Receptors, Scavenger; D020218:Response Elements; D047488:Retinoid X Receptors; D000077154:Rosiglitazone; D051122:Scavenger Receptors, Class B; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists* / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D018955:CD36 Antigens; D004268:DNA-Binding Proteins; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; C496593:Hnf4a protein, mouse; C403128:MLX protein, human; D008565:Membrane Proteins; D010750:Phosphoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D018168:Receptors, Retinoic Acid; D051116:Receptors, Scavenger; D047488:Retinoid X Receptors; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C501970:Tcfl4 protein, mouse; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone