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 glycoprotein that mediates selective uptake and efflux of sterols from high density lipoproteins (HDL) to cells. A Chinese hamster ovary cell line that is deficient in functional LDL receptors, but has high expression levels of recombinant SR-BI (ldlA7-SR-BI), was used to examine the effect of SR-BI on the trafficking of sterols between lipoproteins and cells. To monitor the fate of sterols transported by SR-BI into cells, we measured the incorporation of [14C]oleate into cholesterol esters by acyl-CoA:cholesteryl acyltransferase in the endoplasmic reticulum. We show that incubation of ldlA7-SRBI cells with either LDL or HDL resulted in an equally dramatic increase in the formation of [14C]oleate-labeled cholesterol esters. The lipoprotein-stimulated, SR-BI-dependent 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 free cholesterol to ldlA7-SRBI cells also stimulated cholesterol ester formation in a chloroquine-sensitive fashion. We also show that SR-BI mediates the efflux of endogenously synthesized sterols from the cell membrane. From these studies we conclude that, in the absence of the LDL receptor, overexpression of SR-BI can mediate significant transport of sterols between lipoproteins and the endoplasmic reticulum of cells.
Stangl
H
H
Departments of Internal Medicine and Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
Cao
G
G
Wyne
K L
KL
Hobbs
H H
HH
D000143:Acids / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002738:Chloroquine / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000096:biosynthesis*; D006224:Cricetinae; D004951:Esterification; D008074:Lipoproteins / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D019301:Oleic Acid / Q000378:metabolism; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000378:metabolism*; D051116:Receptors, Scavenger; D011994:Recombinant Proteins / Q000378:metabolism; D051122:Scavenger Receptors, Class B; D002785:Sterol O-Acyltransferase / Q000378:metabolism; D013261:Sterols / Q000378:metabolism
D000143:Acids; D018955:CD36 Antigens; D002788:Cholesterol Esters; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D013261:Sterols; D019301:Oleic Acid; D002738:Chloroquine; D002784:Cholesterol; D002785:Sterol O-Acyltransferase