SCAVENGER RECEPTOR, CLASS-B, TYPE I-DEPENDENT STIMULATION OF CHOLESTEROL ESTERIFICATION BY HIGH-DENSITY-LIPOPROTEINS, LOW-DENSITY LIPOPROTEINS, AND NONLIPOPROTEIN CHOLESTEROL

Scavenger receptor, class B, type I (SR-BI) is a cell surface glycopro tein that mediates selective uptake and efflux of sterols from high de nsity lipoproteins (HDL) to cells. A Chinese hamster ovary cell line t hat is deficient in functional LDL receptors, but has high expression levels of recombinant SR-BI (IdlA7-SR-BI), was used to examine the eff ect of SR-BI on the trafficking of sterols between lipoproteins and ce lls. To monitor the fate of sterols transported by SR-BI into cells, w e measured the incorporation of [C-14]oleate into cholesterol esters b y acyl-CoA:cholesteryl acyltransferase in the endoplasmic reticulum, W e show that incubation of IdlA7-SRBI cells with either LDL or HDL resu lted in an equally dramatic increase in the formation of [C-14]oleate- labeled cholesterol esters, The lipoprotein-stimulated, SR-BI-dependen t increase in cholesterol esterification was inhibited by chloroquine, The uptake of sterols and their incorporation into cholesterol esters by SR-BI from LDL was largely a selective process. The addition of fr ee cholesterol to IdlA7-SRBI cells also stimulated cholesterol ester f ormation in a chloroquine-sensitive fashion. We also show that SR-BI m ediates the efflux of endogenously synthesized sterols from the cell m embrane. From these studies we conclude that, in the absence of the LD L receptor, overexpression of SR-BI can mediate significant transport of sterols between lipoproteins and the endoplasmic reticulum of cells .