Key points are not available for this paper at this time.
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 14Coleate 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 14Coleate-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. 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 14Coleate 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 14Coleate-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. scavenger receptor, class B, type I acyl-CoA:cholesteryl acyltransferase bovine serum albumin Chinese hamster ovary Dulbecco's modified Eagle's medium endoplasmic reticulum high density lipoprotein low density lipoprotein LDL receptor-related protein newborn calf lipoprotein-deficient serum phosphate-buffered saline. Scavenger receptor, class B, type I (SR-BI)1 is an ∼82-kDa, palmitylated, cell surface glycoprotein that binds high density and low density lipoproteins (HDL and LDL) with high affinity (1Acton S.L. Rigotti A. Landschulz K.T. Xu S. Hobbs H.H. Krieger M. Science. 1996; 271: 518-520Crossref PubMed Scopus (2011) Google Scholar, 2Acton S.L. Scherer P.E. Lodish H.F. Krieger M. J. Biol. Chem. 1994; 269: 21003-21009Abstract Full Text PDF PubMed Google Scholar, 3Babitt J. Trigatti B. Rigotti A. Smart E.J. Anderson R.G.W. Xu S. Krieger M. J. Biol. Chem. 1997; 272: 13242-13249Abstract Full Text Full Text PDF PubMed Scopus (337) Google Scholar). Expression of SR-BI in cultured cells is associated with the selective transfer of lipid, but not apoproteins from HDL to cells (1Acton S.L. Rigotti A. Landschulz K.T. Xu S. Hobbs H.H. Krieger M. Science. 1996; 271: 518-520Crossref PubMed Scopus (2011) Google Scholar). SR-BI is expressed at high levels in the liver and in the major steroid-producing regions of the adrenal gland (zona fasiculata and zona reticularis), ovary (corpus luteum), and testes (interstitial cells) of rodents (4Landschulz K.T. Pathak R.K. Rigotti A. Krieger M. Hobbs H.H. J. Clin. Invest. 1996; 98: 984-995Crossref PubMed Scopus (470) Google Scholar, 5Rigotti A. Edelman E.R. Seifert P. Iqbal S.N. DeMattos R.B. Temel R.E. Krieger M. Williams D.L. J. Biol. Chem. 1996; 271: 33545-33549Abstract Full Text Full Text PDF PubMed Scopus (205) Google Scholar, 6Wang N. Weng W. Breslow J.L. Tall A.R. J. Biol. Chem. 1996; 271: 21001-21004Abstract Full Text Full Text PDF PubMed Scopus (192) Google Scholar). Levels of SR-BI are regulated by adrenocorticotrophic hormone (5Rigotti A. Edelman E.R. Seifert P. Iqbal S.N. DeMattos R.B. Temel R.E. Krieger M. Williams D.L. J. Biol. Chem. 1996; 271: 33545-33549Abstract Full Text Full Text PDF PubMed Scopus (205) Google Scholar, 6Wang N. Weng W. Breslow J.L. Tall A.R. J. Biol. Chem. 1996; 271: 21001-21004Abstract Full Text Full Text PDF PubMed Scopus (192) Google Scholar, 7Temel R.E. Trigatti B. DeMattos R.B. Azhar S. Krieger M. Williams D.L. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 13600-13605Crossref PubMed Scopus (210) Google Scholar) and human chorionic gonadotropin (4Landschulz K.T. Pathak R.K. Rigotti A. Krieger M. Hobbs H.H. J. Clin. Invest. 1996; 98: 984-995Crossref PubMed Scopus (470) Google Scholar), which stimulate synthesis of corticosteroids by the adrenal gland and testosterone by the testes, respectively. This tissue pattern of expression and regulation of SR-BI in rodents is consistent with SR-BI being the functionally well characterized HDL receptor that mediates uptake of cholesterol esters in steroidogenic tissues and the liver (8Balasubramaniam S. Goldstein J.L. Faust J.R. Brunschede G.Y. Brown M.S. J. Biol. Chem. 1977; 252: 1771-1779Abstract Full Text PDF PubMed Google Scholar, 9Andersen J.M. Dietschy J.M. Biochem. Biophys. Res. Commun. 1976; 72: 880-885Crossref PubMed Scopus (32) Google Scholar, 10Glass C. Pittman R.C. Civen M. Steinberg D. J. Biol. Chem. 1985; 260: 744-750Abstract Full Text PDF PubMed Google Scholar, 11Glass C. Pittman R.C. Weinstein D.B. Steinberg D. Proc. Natl. Acad. Sci. U. S. A. 1983; 80: 5435-5439Crossref PubMed Scopus (423) Google Scholar). The phenotype of mice lacking functional SR-BI (SR-BI −/− mice) confirms the central role of this receptor in HDL metabolism of rodents;SR-BI −/− mice accumulate large, cholesterol ester-rich HDL particles in their plasma and have a greater than 2-fold increase in plasma HDL-cholesterol levels (12Rigotti A. Trigatti B.L. Penman M. Rayburn H. Herz J. Krieger M. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 12610-12615Crossref PubMed Scopus (761) Google Scholar). The mechanism by which SR-BI delivers cholesterol esters to cells is unknown, but it appears different from the well characterized LDL receptor endocytic pathway (13Brown M.S. Goldstein J.L. Science. 1986; 232: 34-47Crossref PubMed Scopus (4383) Google Scholar). LDL binds to LDL receptors, which are clustered in coated pits on the cell surface. The lipoprotein particles, together with the receptors, are taken up and delivered to endosomes, where the receptors and ligands dissociate, and the receptors are recycled to the cell surface. LDL particles are then transported to lysosomes, where the protein components of the lipoproteins are degraded and the cholesterol esters are hydrolyzed by acid lipase. Free cholesterol released from the particle is transported across the lysosomal membrane, a process that requires NPC1, the gene defective in the lysosomal storage disease Nieman-Pick, type C (14Carstea E.D. Morris J.A. Coleman K.G. Loftus S.K. Zhang D. Cummings C. Gu J. Rosenfeld M.A. Pavan W.J. Krizman D.B. Nagle J. Polymeropoulos M.H. et al.Science. 1997; 277: 228-231Crossref PubMed Scopus (1230) Google Scholar). The lipoprotein-derived cholesterol that enters the endoplasmic reticulum (ER) is re-esterified by acyl-CoA:cholesteryl acyltransferase (ACAT) and stored as cholesterol esters in lipid droplets within the cell (15Chang T.Y. Chang C.C.Y. Cheng D. Annu. Rev. Biochem. 1997; 66: 613-638Crossref PubMed Scopus (442) Google Scholar). In contrast to the LDL receptor, SR-BI is concentrated in caveolae, which are cholesterol- and sphingomyelin-rich of the cell surface J. Trigatti B. Rigotti A. Smart E.J. Anderson R.G.W. Xu S. Krieger M. J. Biol. Chem. 1997; 272: 13242-13249Abstract Full Text Full Text PDF PubMed Scopus (337) Google Scholar, R.G.W. Annu. Rev. Biochem. PubMed Scopus Google Scholar). HDL binds to SR-BI with high and this is associated with the uptake of cholesterol esters from the lipoprotein the of by a mechanism that (1Acton S.L. Rigotti A. Landschulz K.T. Xu S. Hobbs H.H. Krieger M. Science. 1996; 271: 518-520Crossref PubMed Scopus (2011) Google Scholar). The fate of the that are transported by SR-BI into cells has not it has not lipoprotein-derived transported by SR-BI are In this we have the of SR-BI and sterols by SR-BI are transported from the cell surface to the esterification by (15Chang T.Y. Chang C.C.Y. Cheng D. Annu. Rev. Biochem. 1997; 66: 613-638Crossref PubMed Scopus (442) Google Scholar). We show that SR-BI expression is associated with a dramatic increase in cholesterol We also show that which binds SR-BI with high affinity S.L. Scherer P.E. Lodish H.F. Krieger M. J. Biol. Chem. 1994; 269: 21003-21009Abstract Full Text PDF PubMed Google Scholar, D. D. M.A. M.A. Biol. 1997; PubMed Scopus Google Scholar), is as as HDL in cholesterol esterification in an SR-BI-dependent in cells lacking a functional LDL The uptake of from LDL is largely selective and is not associated with significant of the protein components of the lipoprotein We also show that SR-BI expression cholesterol to cells and to stimulate cholesterol cholesterol uptake is not to cholesterol in The of cholesterol esterification by cholesterol as well as by LDL and HDL the of in the esterification is inhibited by the addition of the cholesterol is as free cholesterol or as of a lipoprotein we that SR-BI mediates the efflux of endogenously synthesized sterols to LDL as well as to The SR-BI by of was to and and into Chinese hamster ovary cells that LDL receptor cells) Krieger M. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar) with the expression of SR-BI the of the of SR-BI A of the cell line with the expression of SR-BI and and studies by the cells with either or an and then with (4Landschulz K.T. Pathak R.K. Rigotti A. Krieger M. Hobbs H.H. J. Clin. Invest. 1996; 98: 984-995Crossref PubMed Scopus (470) Google Scholar). The ldlA7-SRBI cells in in medium A of Dulbecco's modified Eagle's medium and medium with with calf serum and The and ldlA7-SRBI cells at a cell density of in in medium A with calf the cells with phosphate-buffered and with medium A newborn calf lipoprotein-deficient serum from cultured cells (4Landschulz K.T. Pathak R.K. Rigotti A. Krieger M. Hobbs H.H. J. Clin. Invest. 1996; 98: 984-995Crossref PubMed Scopus (470) Google Scholar), and of to to transfer to was as (4Landschulz K.T. Pathak R.K. Rigotti A. Krieger M. Hobbs H.H. J. Clin. Invest. 1996; 98: 984-995Crossref PubMed Scopus (470) Google Scholar) a LDL receptor J. R.C. Brown M.S. Goldstein J.L. J. Biol. Chem. Full Text PDF PubMed Google Scholar), a LDL receptor-related protein R.E. Herz J. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar), or incubation with the the was and the (4Landschulz K.T. Pathak R.K. Rigotti A. Krieger M. Hobbs H.H. J. Clin. Invest. 1996; 98: 984-995Crossref PubMed Scopus (470) Google Scholar). The to at the The of the a and HDL and LDL was by 1986; PubMed Scopus Google Scholar). The lipoproteins and was to and or the lipoproteins used the in this not The cholesterol and protein J. Biol. Chem. Full Text PDF PubMed Google Scholar) of the lipoproteins the of cholesterol to protein and The lipoproteins the J.L. S.K. Brown M.S. 1983; 98: PubMed Scopus Google Scholar), and the from to lipoproteins and being To of cholesterol the cells as that and to the medium on the cells with and in of bovine serum albumin to addition of of or a incubation with the cells with the cells with A and and with and The from the cell and by J.L. S.K. Brown M.S. 1983; 98: PubMed Scopus Google Scholar). The cells in of and the protein was the J. Biol. Chem. Full Text PDF PubMed Google Scholar). The and ldlA7-SRBI cells in medium A with and with 14Coleate The medium was and the The was with and with was to the of by the cells is J.L. S.K. Brown M.S. 1983; 98: PubMed Scopus Google Scholar). The the is expressed in of protein of cell The cell and and by as as that on the medium was and the cells with and with medium A A of of of or and was to well Faust J.R. Brown M.S. Goldstein J.L. J. 1977; PubMed Scopus Google J.R. Goldstein J.L. Brown M.S. Biochem. Biophys. PubMed Scopus Google Scholar). the cells with A and with to incubation in with and either HDL or LDL in the The medium was and the cells with to being by of of the medium and cells the and cells, of the medium and cells as Faust J.R. Brown M.S. Goldstein J.L. J. 1977; PubMed Scopus Google Scholar, J.R. Goldstein J.L. Brown M.S. Biochem. Biophys. PubMed Scopus Google Scholar). To the role of SR-BI of the LDL receptor, we expressed recombinant SR-BI (1Acton S.L. Rigotti A. Landschulz K.T. Xu S. Hobbs H.H. Krieger M. Science. 1996; 271: 518-520Crossref PubMed Scopus (2011) Google Scholar) in cell of functional LDL receptors cells) Krieger M. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). studies and an A pattern of was on the cell surface of the cells not which is consistent with SR-BI being in caveolae, as has J. Trigatti B. Rigotti A. Smart E.J. Anderson R.G.W. Xu S. Krieger M. J. Biol. Chem. 1997; 272: 13242-13249Abstract Full Text Full Text PDF PubMed Scopus (337) Google Scholar). of from the cell line cells and of cells of SR-BI levels of SR-BI in the and cells. The levels of SR-BI up to in the ldlA7-SRBI cells than in the cells. ldlA7-SRBI that expressed of SR-BI are in and A was in of the but was not in the cell The in the cells SR-BI protein that has not LDL receptor was in the cells LDL receptor was in of the cell a of the to a of the cell expressed of R.E. Herz J. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar), cell surface levels of expression of SR-BI not associated with in the levels of a protein of it was that SR-BI mediates selective transport of from HDL into cells (1Acton S.L. Rigotti A. Landschulz K.T. Xu S. Hobbs H.H. Krieger M. Science. 1996; 271: 518-520Crossref PubMed Scopus (2011) Google Scholar), the fate of the lipoprotein-derived has not To SR-BI expression the of sterols from lipoproteins to the cholesterol and ldlA7-SRBI cells with of human HDL or LDL by a incubation with The of cholesterol to cholesterol ester within the was measured by as increase in esterification was in the cells the addition of either LDL or HDL In addition of LDL or HDL to the ldlA7-SRBI cells resulted in a dramatic increase in esterification of lipoprotein to the the of cholesterol esters was with LDL than with the was as a of the of cholesterol to the cells a was with LDL and of 14Coleate and incorporation into and not different between and ldlA7-SRBI with LDL and in the absence of the LDL receptor, SR-BI expression is associated with an increase in cholesterol and LDL is as as HDL as a this as well as the in this the ldlA7-SRBI cells. To that the not a was in the and and the of the was to the of SR-BI protein expressed A of the incorporation of 14Coleate into cholesterol esters in the ldlA7-SRBI cells is in with of of either HDL or LDL the which the cells with 14Coleate an with 14Coleate in the absence of lipoproteins a low of 14Coleate incorporation which not with not A increase in cholesterol esterification was in the cells with either LDL or HDL which is to the low levels of SR-BI in these cells In the ldlA7-SRBI cells, a increase in cholesterol esterification the addition of either LDL or HDL To the effect of SR-BI expression on the of we measured the of cholesterol in the and ldlA7-SRBI cells incubation with or the addition of either LDL or HDL The of cholesterol was in the ldlA7-SRBI cells than the cells with addition of lipoproteins of significant in the of cholesterol was in the cells the addition of LDL and In the ldlA7-SRBI cells was a and increase in cholesterol addition of HDL and respectively. The pathway by which SR-BI expression cholesterol esterification was a that in and their C. B. A. P. Biochem. PubMed Scopus Google Scholar). with to the addition of of HDL or LDL The cells then with 14Coleate A in cholesterol esterification was with the addition of of to the cells cholesterol esterification was at which is to the at which this uptake of LDL by the LDL receptor J.L. Brunschede G.Y. Brown M.S. J. Biol. Chem. Full Text PDF PubMed Google Scholar). To that not the cells with and then with 14Coleate in the or absence of the of cholesterol esters was in the of cells are consistent with SR-BI-dependent stimulated cholesterol esterification the of within the et (1Acton S.L. Rigotti A. Landschulz K.T. Xu S. Hobbs H.H. Krieger M. Science. 1996; 271: 518-520Crossref PubMed Scopus (2011) Google Scholar) that uptake of cholesterol from HDL SR-BI was not to of the protein To SR-BI mediates selective uptake of lipid from LDL as well as we the esterification LDL In cells, esterification was inhibited by cells, which are the cell line the cells, the LDL receptor and SR-BI In esterification of cholesterol was in the LDL cells in the or absence of not In the ldlA7-SRBI cells, which LDL receptors but have levels of the of cholesterol esterification was high and with the addition of chloroquine. The of the protein of the LDL was measured in the In cells, was by addition of but was an high of in these cells. To that lipoprotein particles not in cultured human and cells, the cell line of the cells. A of was with addition of not the of the cells to LDL by was and not to an associated with lipoprotein cells, cells, have to in Goldstein J.L. Brown M.S. J. Biol. Chem. Full Text PDF PubMed Google Scholar), which have an lipid uptake In contrast to the cell line the cells not in the absence or of not levels of in the ldlA7-SRBI cells which was by chloroquine. The of 14Coleate formation to LDL in the ldlA7-SRBI cells was in the cells it was The and was in either the or ldlA7-SRBI cells not these are consistent with SR-BI selective uptake of sterols from LDL as well as HDL To uptake by SR-BI requires the lipid to as of a lipoprotein free cholesterol in was to cells and the incorporation of 14Coleate into cholesterol esters was measured of effect on cholesterol esterification not a increase in cholesterol esterification in the cells and cells not In a increase in cholesterol esterification was in ldlA7-SRBI the esterification was by the addition of To that esterification was to the expression of we of ldlA7-SRBI cells, and The of esterification in these cells to the levels of SR-BI not The of esterification in the ldlA7-SRBI cells was with that with HDL and The increase in esterification between and and the of of 14Coleate in a the not The that SR-BI is to increase the of cholesterol from the medium to the that cholesterol not as of a lipoprotein or by has that expression of recombinant SR-BI in cells is associated with an increase in cholesterol efflux from cells to HDL B. N. M. Tall A.R. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus Google Scholar, B. M. N. Tall A.R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). To SR-BI can cholesterol to LDL as well as to we ldlA7-SRBI cells with and then the cells with of LDL or HDL In the cells, HDL was than LDL as an of cholesterol from the cells SR-BI expression was associated with a increase in efflux of sterols from cells to either HDL or to of the was to the medium than of the in the medium was with that the cholesterol was within lipoproteins not The medium was also by and of the the from the as the cholesterol not The of transfer of cholesterol to either LDL or HDL is in C and of A increase in cholesterol efflux to LDL and HDL was in the cells of the cholesterol to In the ldlA7-SRBI cells, was a increase in efflux that a at The efflux was cholesterol efflux at not In the in the cells in medium in these of the can to in the cell P.E. PubMed Scopus (32) Google Scholar). To SR-BI can mediate the efflux of endogenously synthesized we cells with a of cholesterol in the and then of either LDL or HDL In the ldlA7-SRBI cells, the of cholesterol in the lipoproteins in to the of lipoproteins to the medium the expressed to the of cholesterol to the cells, HDL to a than LDL these not The efflux of an in the cholesterol was also measured by in the lipoproteins incubation with cells and ldlA7-SRBI cells The efflux of that of HDL was a of than was in the medium and low levels of in the cells not The major in this are that SR-BI mediates uptake of from as well as and that this uptake is associated with an increase in cholesterol The cholesterol of the lipoproteins to cells, than their with the of cholesterol esters by the ldlA7-SRBI cells. Free cholesterol cholesterol is as as lipoproteins at cholesterol esterification in the cells cholesterol not associated with lipoproteins SR-BI to mediate uptake by cells. The SR-BI-dependent of cholesterol esterification was inhibited by a that the of we show that SR-BI can mediate efflux of sterols to lipoproteins and efflux of cholesterol from the plasma to as well as HDL B. N. M. Tall A.R. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus Google Scholar, B. M. N. Tall A.R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). SR-BI binds as well as with high affinity S.L. Scherer P.E. Lodish H.F. Krieger M. J. Biol. Chem. 1994; 269: 21003-21009Abstract Full Text PDF PubMed Google Scholar, D. D. M.A. M.A. Biol. 1997; PubMed Scopus Google Scholar). studies that SR-BI not binds LDL but also mediates the transport of sterols from the lipoprotein to cells. SR-BI expression was associated with a dramatic increase in cholesterol esterification and this process was not by significant of the are consistent with in studies which that the receptor that mediates selective uptake of cholesterol esters from HDL in steroidogenic tissues also up sterols from LDL S. A. W. J. Res. Full Text PDF PubMed Google Scholar). and S. Azhar S. A. 1996; PubMed Scopus Google Scholar) that HDL stimulated cholesterol esterification in cells, which we high levels of SR-BI (4Landschulz K.T. Pathak R.K. Rigotti A. Krieger M. Hobbs H.H. J. Clin. Invest. 1996; 98: 984-995Crossref PubMed Scopus (470) Google Scholar). The of are consistent with SR-BI being the of cholesterol We show that, in the absence of a functional LDL receptor, LDL is as as HDL at cholesterol ester formation in cells and P.E. PubMed Scopus (32) Google Scholar) have that free cholesterol is taken up by a selective mechanism that is of the LDL receptor, and this uptake by this uptake mechanism is to have in LDL from the as is by the high plasma levels of LDL in functional LDL receptor the these not have significant of which by the of SR-BI as a receptor that of to steroidogenic tissues to and the The LDL and HDL particles used in these in that a lipid, than is by the the that cholesterol was to stimulate cholesterol esterification in an SR-BI-dependent that and not are the ligands this are consistent with in studies that selective uptake of lipoprotein sterols by tissues not the of R.C. D. J. Biol. Chem. Full Text PDF PubMed Google Scholar). In this Xu et S. M. Rigotti A. Krieger M. J. Res. 1997; Full Text PDF PubMed Google Scholar) that SR-BI also binds and The of SR-BI to and is a that this receptor with a in the class scavenger receptor binds type as well as H. 80: PubMed Google Scholar). SR-BI and and LDL as well as S.L. Scherer P.E. Lodish H.F. Krieger M. J. Biol. Chem. 1994; 269: 21003-21009Abstract Full Text PDF PubMed Google Scholar, A. S.L. Krieger M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). of to the of these that to with a of SR-BI expression was associated with a increase in cholesterol esterification free cholesterol was to the medium it has that the addition of low of cholesterol to not in an increase in cholesterol esterification by the cells J. Biol. Chem. Full Text PDF PubMed Google Scholar). addition of levels of cholesterol stimulate cholesterol esterification in J. Biol. Chem. Full Text PDF PubMed Google Scholar). at greater than which the pathway by which the enters cells than by as has J. Biol. Chem. Full Text PDF PubMed Google Scholar). increase in cholesterol esterification was we the cells with or cholesterol not of cholesterol to the medium resulted in a 2-fold increase in esterification in the and ldlA7-SRBI cells was addition of high of which are associated with that we a significant increase in 14Coleate formation in the cells. The of this is not SR-BI mediates uptake from cholesterol that are in tissues and The SR-BI-dependent of cholesterol esterification by free as well as by lipoprotein-derived was inhibited by chloroquine. this we can as to the with SR-BI on the cell membrane. SR-BI in caveolae, and sterols the cell this which is the major protein in caveolae, binds cholesterol M. J. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar) and can stimulated to between the cell membrane, the and the E.J. Anderson R.G.W. J. Biol. 1994; PubMed Scopus Google Scholar). trafficking from the cell membrane, a process to as requires of the which to by C. Anderson R.G.W. Res. 1996; PubMed Scopus Google Scholar). SR-BI the of sterols endocytic S. Azhar S. A. 1996; PubMed Scopus Google Scholar, P.E. J. Res. 1997; Full Text PDF PubMed Google Scholar, P.E. 1996; PubMed Scopus Google Scholar). are to have a high cholesterol Annu. Rev. Biol. PubMed Scopus Google Scholar) and uptake into this is by chloroquine. esters by the selective uptake pathway accumulate in the to being hydrolyzed by a cholesterol Pittman R.C. Biophys. PubMed Scopus Google Scholar). and Pittman Pittman R.C. Biophys. PubMed Scopus Google Scholar) that not of these cholesterol esters. also that in in which have acid the cholesterol esters are hydrolyzed not the cell the endocytic pathway Annu. Rev. Biol. PubMed Scopus Google Scholar). cholesterol esters are the major of sterols esterification in the cells, the cholesterol esters an to the being We not the increase in cholesterol esterification in cells is to the uptake of cholesterol or cholesterol esters from lipoprotein In we have that cholesterol is into cholesterol esters in an SR-BI-dependent not are in to the of cholesterol and cholesterol esters to the cholesterol esterification in the ldlA7-SRBI cells. SR-BI not mediates the of from lipoproteins but also efflux of cholesterol in the cell B. N. M. Tall A.R. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus Google Scholar, B. M. N. Tall A.R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The transport of synthesized as well as to lipoproteins is by SR-BI is that the of the transfer of between and lipoproteins is by the of lipid in as well as the of into the and We and and We Krieger the cells and the SR-BI
Stangl et al. (Sun,) studied this question.