Regulation by vitamin E of the scavenger receptor BI in rat liver and HepG2 cells.
The scavenger receptor class B type I (SR-BI) mediates the selective uptake of cholesterol and cholesteryl ester (CE) from high density lipoprotein (HDL) into cells. The high expression in liver and steroidogenic tissues is compatible with a role of SR-BI in reverse cholesterol transport and steroid hormone synthesis. Ways of regulation thus far described include induction by trophic hormones via cAMP-activated protein kinase A (PKA) and the effects of cellular and plasma cholesterol. Here we show that vitamin E (vitE) has a major effect on the expression of SR-BI in rat liver and in a human hepatoma-derived cell line, HepG2. Feeding rats a vitE-depleted diet resulted in an 11-fold increase in the SR-BI protein level in liver tissue. This effect was readily reversed by feeding a vitE-enriched chow. In HepG2 cells, the expression of the human SR-BI homolog was reduced when the vitE content was increased by incubating the cells with vitE-loaded HDL or with phosphatidylcholine/vitE vesicles. The downregulation of human SR-BI (hSR-BI) was accompanied by a reduced level of protein kinase C (PKC) in the particulate cell fraction, and PKC inhibition decreased the expression of hSR-BI and the uptake of vitE and cholesterol from HDL. Our results are consistent with the view that the cellular level of vitE exerts a tight control over the expression of SR-BI. Furthermore, the inhibitory effect of vitE on PKC seems to be involved in the signaling pathway.
Witt
W
W
Department of Neonatology, University Hospital Charité, Humboldt University, 10098 Berlin, Germany.
Kolleck
I
I
Fechner
H
H
Sinha
P
P
Rüstow
B
B
D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000494:pharmacology*; D014811:Vitamin E Deficiency / Q000378:metabolism
D018955:CD36 Antigens; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B; D014810:Vitamin E; D011493:Protein Kinase C