Involvement of caveolin-1 in cholesterol enrichment of high density lipoprotein during its assembly by apolipoprotein and THP-1 cells

Abstract

High density lipoprotein (HDL) is assembled by interaction of apolipoprotein A-I with human monocytic leukemia cell line THP-1 by removing cellular cholesterol and phospholipid. Although the HDL formed with undifferentiated THP-1 cells contained only phosphatidylcholine and almost no cholesterol, the cells differentiated with phorbol 12-myristate 13-acetate (PMA) generated HDL enriched in cholesterol. The extent of cholesterol enrichment related to the cellular cholesterol level in the differentiated cells, but only weakly in the undifferentiated cells. In contrast, the differentiation had no influence on the diffusion-mediated cellular cholesterol efflux. The undifferentiated cells expressed the messages of ATP-binding cassette transporter 1 and caveolin-1, at low levels, and the PMA-induced differentiation resulted in substantial expression of both messages. Caveolin-1 protein expression was also highly induced by the PMA treatment of THP-1 cells. When the cells were treated with the antisense DNA of caveolin-1 and differentiated, both caveolin-1 synthesis and cholesterol incorporation into the HDL were reduced in parallel to generate the cholesterol-poor HDL. We concluded that caveolin-1 is involved in enrichment with cholesterol of the HDL generated by the apolipoprotein-cell interaction. This function is independent of the assembly of HDL particles with cellular phospholipid and of nonspecific, diffusion-mediated efflux of cellular cholesterol.—Arakawa, R., S. Abe-Dohmae, M. Asai, J-i. Ito, and S. Yokoyama. Involvement of caveolin-1 in cholesterol enrichment of high density lipoprotein during its assembly by apolipoprotein and THP-1 cells. J. Lipid Res. 2000. 41: 1952–1962. High density lipoprotein (HDL) is assembled by interaction of apolipoprotein A-I with human monocytic leukemia cell line THP-1 by removing cellular cholesterol and phospholipid. Although the HDL formed with undifferentiated THP-1 cells contained only phosphatidylcholine and almost no cholesterol, the cells differentiated with phorbol 12-myristate 13-acetate (PMA) generated HDL enriched in cholesterol. The extent of cholesterol enrichment related to the cellular cholesterol level in the differentiated cells, but only weakly in the undifferentiated cells. In contrast, the differentiation had no influence on the diffusion-mediated cellular cholesterol efflux. The undifferentiated cells expressed the messages of ATP-binding cassette transporter 1 and caveolin-1, at low levels, and the PMA-induced differentiation resulted in substantial expression of both messages. Caveolin-1 protein expression was also highly induced by the PMA treatment of THP-1 cells. When the cells were treated with the antisense DNA of caveolin-1 and differentiated, both caveolin-1 synthesis and cholesterol incorporation into the HDL were reduced in parallel to generate the cholesterol-poor HDL. We concluded that caveolin-1 is involved in enrichment with cholesterol of the HDL generated by the apolipoprotein-cell interaction. This function is independent of the assembly of HDL particles with cellular phospholipid and of nonspecific, diffusion-mediated efflux of cellular cholesterol.—Arakawa, R., S. Abe-Dohmae, M. Asai, J-i. Ito, and S. Yokoyama. Involvement of caveolin-1 in cholesterol enrichment of high density lipoprotein during its assembly by apolipoprotein and THP-1 cells. J. Lipid Res. 2000. 41: 1952–1962. Cholesterol is not metabolized in peripheral cells except for the limited catabolism by sterol 27-hydroxylase and steroidogenesis in certain specific organs. Most cellular cholesterol is therefore removed and transported to the liver for its conversion to bile acids. High density lipoprotein (HDL) is believed to play a central role in this pathway. Two major mechanisms are proposed for the initial step of this transport system (1Yokoyama S. Apolipoprotein-mediated cellular cholesterol efflux.Biochim. Biophys. Acta. 1998; 1392: 1-15Google Scholar); nonspecific diffusion of cholesterol out of the cells through the aqueous phase and assembly of HDL by apolipoprotein with cellular lipids. Mutations were identified in ATP-binding cassette transporter 1 (ABC1) in patients with genetic HDL deficiency (2Brools-Wilson A. Marcil M. Clee S.M. Zhang L-H. Roomp K. van Dam M. Yu L. Brewer C. Collins J.A. Molhuizen H.O.F. Loubser O. Ouelette B.F.F. Fichter K. Ashbourne-Excoffon K.J.D. Sensen C.W. Schere S. Mott S. Denis M. Martindale D. Frohlich J. Morgan K. Koop B. Pimstone S. Kastelein J.J.P. Genest Jr., J. Hayden M.R. Mutations of ABC 1 in Tangier disease and familial high density lipoprotein deficiency.Nat. Genet. 1999; 22: 336-345Google Scholar, 3Bodzioch M. Orso E. Klucken J. Langmann T. Böttcher A. Diederich W. Drobnik W. Barlage S. Büchler C. Porsch-Özcürümez M. Kaminski W.E. Hahmann H.W. Oette K. Rothe G. Aslanidis C. Lackner K.J. Schmitz G. The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease.Nat. Genet. 1999; 22: 347-351Google Scholar, 4Rust S. Rosier M. Funke H. Real J. Amoura Z. Piette J-C. Delueze J-F. Brewer H.B. Duverger N. Denefle P. Assmann G. Tangier disease is caused by mutations in the gene encoding ATP-cassette transporter 1.Nat. Genet. 1999; 22: 352-355Google Scholar, 5Lawn R.M. Wade D.P. Garvin M.R. Wang X. Schwartz K. Porter J.G. Seilhamer J.J. Vaughan A.M. Oram J.F. The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway.J. Clin. Invest. 1999; 104: R25-R31Google Scholar, 6Remaley A.T. Rust S. Rosier M. Knapper C. Naudin L. Broccardo C. Peterson K.M. Koch C. Arnould I. Prades C. Duverger N. Funke H. Assmann G. Dinger M. Dean M. Chimini G. Santamarina-Fojo S. Fredrickson D.S. Denefle P. Brewer Jr., H.B. Human ATP-binding cassette transporter 1 (ABC1): genomic organization and identification of the genetic defect in the original Tangier disease kindred.Proc. Natl. Acad. Sci. USA. 1999; 96: 12685-12690Google Scholar), whose cells demonstrate impairment of the latter mechanism (7Francis G.A. Knopp R.H. Oram J.F. Defective removal of cellular cholesterol and phospholipids by apolipoprotein A-I in Tangier disease.J. Clin. Invest. 1995; 96: 78-87Google Scholar, 8Remaley A.T. Schumacher U.K. Stonik J.A. Farsi B.D. Nazih H.B. Brewer Jr., H.B. cholesterol transport Tangier disease and of on lipid Scholar, J.F. J. in apolipoprotein-mediated removal of cellular by of human and its by of with Tangier disease Lipid Res. 1999; Scholar, A. A. S. M. Kastelein J.J.P. J. Real G. G. Assmann G. and of Tangier disease patients are in phospholipids apolipoprotein Lipid Res. 1998; This the that the assembly of HDL by apolipoprotein-cell interaction is a major of HDL in the (1Yokoyama S. Apolipoprotein-mediated cellular cholesterol efflux.Biochim. Biophys. Acta. 1998; 1392: 1-15Google Scholar, J.F. S. Apolipoprotein-mediated removal of cellular cholesterol and Lipid Res. the role of ABC1 in this not and its function in cholesterol transport is proposed on the of the to the function of ABC The of cholesterol Genet. 1999; 22: HDL assembly by with cellular H. S. of with of high density and of cellular Scholar), that this at independent (1Yokoyama S. Apolipoprotein-mediated cellular cholesterol efflux.Biochim. Biophys. Acta. 1998; 1392: 1-15Google Scholar); is a cellular interaction for apolipoprotein to HDL particles with cellular phospholipid H. S. Involvement of cellular in apolipoprotein-mediated cellular cholesterol efflux.Biochim. Biophys. Acta. 1995; Scholar, M. M. C. E. apolipoprotein and cholesterol efflux cell line to apolipoprotein Scholar, M. S. of apolipoprotein-mediated cellular lipid efflux by Scholar, L. Apolipoprotein-mediated cellular cholesterol and phospholipid efflux on a Lipid Res. and the is a specific cholesterol system for its incorporation into HDL Oram J.F. a of high density lipoprotein efflux of Scholar, S. of cholesterol incorporation into apolipoprotein-mediated cellular lipid efflux in 1995; Scholar, M. S. by protein of apolipoprotein-mediated cholesterol efflux in Scholar, Cholesterol efflux by is cellular efflux by Lipid Res. In to the mechanism in this specific cholesterol that undifferentiated human monocytic leukemia cell with apolipoprotein A-I and HDL with cellular phospholipid but no cholesterol. the cells are differentiated by phorbol to the to S. S. A. of a human monocytic leukemia cell line and apolipoprotein and lipoprotein Biophys. Res. Scholar, H. H. S. S. A. of low density lipoprotein on the cells of human monocytic leukemia cell line Biophys. Res. Scholar, M. S. A. of the apolipoprotein gene in a human cell Scholar, N. M. S. T. A. of of 1 to of in a cell 1998; Scholar), HDL is generated by the the of a to cholesterol into the HDL. In the the mechanism of this THP-1 cells were in its in a of and differentiation of THP-1 into the cells were in a at a density of in the of phorbol 12-myristate 13-acetate (PMA) for H. H. S. S. A. of low density lipoprotein on the cells of human monocytic leukemia cell line Biophys. Res. except for the to the of the of the PMA The was with with and for a The undifferentiated cells were in and for and in a at a cell density of The differentiated and undifferentiated cells were in the of human with a of S. S. A. of lipid on of with Scholar), in for The lipid in the and the cells was with and for of cholesterol and phospholipid the of phosphatidylcholine and the cells were with for the with H. S. of with of high density and of cellular of phospholipid was the lipid in the was and by The cells were in for protein by the The of the was at for at in a and the was This was on of of and in for a at for at the was the into The of cholesterol and phospholipid the density of were of into in the cells was G.A. Oram J.F. of HDL the of cellular by a mechanism independent of sterol of the cells with at for the cells were with for 1 The incorporation of into the was lipid and by The was THP-1 cells to its of and by and in The cells were in and at for to the to was and The was in and at for and the was at for The was and at for 1 to the the This of protein was with of cholesterol and in with at for was in of and with of protein in at for and the was by of at for in was the lipid was by cholesterol for the the cholesterol was by the The undifferentiated cells were in at a density of in the of a of the antisense and DNA for human caveolin-1, by contained cells the was out in a at and the cells were treated with PMA for The lipid was The cells were in and by at for The and were by of the cells in and at the and the of the of to during transport to the cell Scholar), the cells were in of 1 1 1 and 1 and of was The was for with of and at for The was at for and the was in the and on the at for 1 the at the was and in the and the and with of and at for The was with and the was by at for The protein of was by the were by and to a The was in at with the was in and with with The was and caveolin-1 was by a was by the the cells were in the of and and was in the aqueous phase by and was with and the was with and was by the at to the was in was the and the of caveolin-1 and ABC1 were in a system and by for by was also The was by The of the was by the with to the of and the of the 1 the of the differentiation of THP-1 cells by PMA on the removal of cellular cholesterol by The cholesterol removal was induced by the PMA treatment of the cells in a to HDL assembly was therefore in THP-1 cells of PMA treatment When was to the phospholipid was into the the cells in a in both the undifferentiated and differentiated with a in the differentiated Cholesterol by was the undifferentiated cells, a substantial of cholesterol was by differentiated cells. of the phospholipid in the that the of phosphatidylcholine was by was in the cholesterol The HDL particles that in the during the were by density The HDL generated undifferentiated cells contained a of cholesterol the HDL differentiated cells was in cholesterol. The in HDL cholesterol was in of the to of by THP-1 cells. and of and cholesterol into 1 of undifferentiated and differentiated THP-1 cells and of cell protein in the of and of phosphatidylcholine and undifferentiated and differentiated THP-1 cells and and of the of undifferentiated and differentiated THP-1 cells and of cell with The the of for are by for The in and are the of the of for a cholesterol removal was in to the of cellular cholesterol. cells contained a of and cholesterol undifferentiated cells, and of cholesterol, the cells had cholesterol the cells cholesterol was by in differentiated cells, cellular cholesterol not in undifferentiated cells, the of its removal by The cholesterol removal differentiated cells cell cholesterol When cholesterol was into differentiated cells by with low density lipoprotein to the extent that cellular cholesterol was cell the was to cell protein not phospholipid removal not by cell cholesterol level the HDL generated by this was enriched in cholesterol the cellular cholesterol in the differentiated THP-1 cells. were with the by and M.R. A-I cholesterol and apolipoprotein THP-1 Lipid Res. 1999; Cholesterol undifferentiated cells was to phospholipid was the in differentiated cells Cholesterol of undifferentiated cells resulted only in a in cellular The cholesterol and the in cellular cholesterol by not a level of cholesterol of undifferentiated cells on cholesterol removal and cellular cholesterol. The cells were with for and with for cholesterol in the and and cholesterol in the cell were in The cholesterol was the and cholesterol. protein was of the cells and of the cellular cholesterol by was incorporation of into was by cells The of the was by independent by differentiation and The was by the and The by the PMA treatment and the cholesterol the the and This with the of cholesterol by only in differentiated cells, the undifferentiated cells not to the of cholesterol incorporation into the HDL of into and of the in undifferentiated and differentiated THP-1 cells were with for at and was to the for the for 1 to its incorporation into cell The in the cells was with the the cholesterol by incorporation of into and by of to the in The of the The are by the and in to the cholesterol for the and The cells were with for at and was to the for the for 1 to its incorporation into cell The in the cells was with the the cholesterol by incorporation of into and by of to the in The of the The are by the and in to the cholesterol for the and in a cholesterol by and by lipid cholesterol was also induced by cellular differentiation by In contrast, cholesterol induced by the lipid by nonspecific diffusion was not by The with was with the that the to generate HDL cellular is not highly specific to but is by H. H. A. S. for to generate HDL and to cellular lipid Scholar, of lipid to on of cellular Lipid Res. The of cholesterol by cellular differentiation is limited to the apolipoprotein-mediated and is not to nonspecific diffusion of cholesterol the cellular the of gene expression by cellular The of ABC1 and caveolin-1 are the of messages are in the cells differentiated by the of ABC1 and caveolin-1 Caveolin-1 protein also cell differentiation by by When expression was caveolin-1 was in the of ABC1 and caveolin-1 in THP-1 cells by differentiation with of the of the was by with a and for The the and of of the of the was by with a and for The the and of in a the role of caveolin-1 that of ABC1 in cholesterol the cells were treated with antisense DNA caveolin-1 of caveolin-1 protein was by the phospholipid by was not by the antisense the cholesterol the cells was of cholesterol into the was cell protein the cells and cell protein the antisense cells, the of the independent of the in the lipid that of the cells, the of cholesterol-poor HDL in the The of treatment was by density The of treatment contained HDL generated by the and the HDL generated with the antisense cells was in cholesterol. cholesterol is in and cholesterol was the in cells treated with and and no in cholesterol was induced by in of cells. the cholesterol by in the cells treated with and DNA but not in treated with antisense of cell cholesterol with caveolin-1 protein expression level by antisense DNA with to the cells. The in cholesterol was with the level of caveolin-1 protein of the with of cells treated with and The were to in The were the to the and cholesterol were for density The in cellular cholesterol to HDL assembly in THP-1 cells treated with and The were to in and the the of a by in cholesterol and caveolin-1 expression by The with the antisense cells are expressed the to with cells in the The of independent of The line the the We that the differentiation of THP-1 cells by phorbol resulted in the cholesterol enrichment of the HDL that is generated by the apolipoprotein-cell independent of the diffusion-mediated cellular cholesterol efflux. Two to in cholesterol transport are induced in the to mutated in genetic HDL (2Brools-Wilson A. Marcil M. Clee S.M. Zhang L-H. Roomp K. van Dam M. Yu L. Brewer C. Collins J.A. Molhuizen H.O.F. Loubser O. Ouelette B.F.F. Fichter K. Ashbourne-Excoffon K.J.D. Sensen C.W. Schere S. Mott S. Denis M. Martindale D. Frohlich J. Morgan K. Koop B. Pimstone S. Kastelein J.J.P. Genest Jr., J. Hayden M.R. Mutations of ABC 1 in Tangier disease and familial high density lipoprotein deficiency.Nat. Genet. 1999; 22: 336-345Google Scholar, 3Bodzioch M. Orso E. Klucken J. Langmann T. Böttcher A. Diederich W. Drobnik W. Barlage S. Büchler C. Porsch-Özcürümez M. Kaminski W.E. Hahmann H.W. Oette K. Rothe G. Aslanidis C. Lackner K.J. Schmitz G. The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease.Nat. Genet. 1999; 22: 347-351Google Scholar, 4Rust S. Rosier M. Funke H. Real J. Amoura Z. Piette J-C. Delueze J-F. Brewer H.B. Duverger N. Denefle P. Assmann G. Tangier disease is caused by mutations in the gene encoding ATP-cassette transporter 1.Nat. Genet. 1999; 22: 352-355Google Scholar, 5Lawn R.M. Wade D.P. Garvin M.R. Wang X. Schwartz K. Porter J.G. Seilhamer J.J. Vaughan A.M. Oram J.F. The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway.J. Clin. Invest. 1999; 104: R25-R31Google Scholar, 6Remaley A.T. Rust S. Rosier M. Knapper C. Naudin L. Broccardo C. Peterson K.M. Koch C. Arnould I. Prades C. Duverger N. Funke H. Assmann G. Dinger M. Dean M. Chimini G. Santamarina-Fojo S. Fredrickson D.S. Denefle P. Brewer Jr., H.B. Human ATP-binding cassette transporter 1 (ABC1): genomic organization and identification of the genetic defect in the original Tangier disease kindred.Proc. Natl. Acad. Sci. USA. 1999; 96: 12685-12690Google Scholar), and caveolin-1, cholesterol transport to the role for in transport of cholesterol to Scholar, A. of a in cholesterol 1998; The expression of caveolin-1 was by antisense DNA treatment of differentiated cells, and cholesterol incorporation was in the HDL generated by the apolipoprotein-cell interaction. PMA treatment not influence cellular cholesterol efflux by a nonspecific diffusion-mediated of cellular cholesterol by cell differentiation was to the apolipoprotein-mediated and was independent of the at the cellular of the cholesterol that nonspecific diffusion through the aqueous phase to lipid the of the PMA treatment to a in cholesterol, and is related to of specific cholesterol for the apolipoprotein-mediated Apolipoprotein-mediated cellular cholesterol removal is a cellular cholesterol mechanism the nonspecific by diffusion (1Yokoyama S. Apolipoprotein-mediated cellular cholesterol efflux.Biochim. Biophys. Acta. 1998; 1392: 1-15Google This HDL particles with apolipoprotein and cellular lipid and a cellular interaction for apolipoprotein H. S. Involvement of cellular in apolipoprotein-mediated cellular cholesterol efflux.Biochim. Biophys. Acta. 1995; Scholar, M. M. C. E. apolipoprotein and cholesterol efflux cell line to apolipoprotein Scholar, M. S. of apolipoprotein-mediated cellular lipid efflux by Scholar, L. Apolipoprotein-mediated cellular cholesterol and phospholipid efflux on a Lipid Res. and cholesterol transport system specific for incorporation of cholesterol into HDL Oram J.F. a of high density lipoprotein efflux of Scholar, S. of cholesterol incorporation into apolipoprotein-mediated cellular lipid efflux in 1995; Scholar, M. S. by protein of apolipoprotein-mediated cholesterol efflux in Scholar, Cholesterol efflux by is cellular efflux by Lipid Res. The also a major of by the impairment of this in Tangier the genetic HDL deficiency (7Francis G.A. Knopp R.H. Oram J.F. Defective removal of cellular cholesterol and phospholipids by apolipoprotein A-I in Tangier disease.J. Clin. Invest. 1995; 96: 78-87Google Scholar, 8Remaley A.T. Schumacher U.K. Stonik J.A. Farsi B.D. Nazih H.B. Brewer Jr., H.B. cholesterol transport Tangier disease and of on lipid Scholar, J.F. J. in apolipoprotein-mediated removal of cellular by of human and its by of with Tangier disease Lipid Res. 1999; Scholar, A. A. S. M. Kastelein J.J.P. J. Real G. G. Assmann G. and of Tangier disease patients are in phospholipids apolipoprotein Lipid Res. 1998; Scholar), and by the of this by the M. S. of apolipoprotein-mediated cellular lipid efflux by This was by the that the gene defect in Tangier disease is in the transporter protein ABC1 (2Brools-Wilson A. Marcil M. Clee S.M. Zhang L-H. Roomp K. van Dam M. Yu L. Brewer C. Collins J.A. Molhuizen H.O.F. Loubser O. Ouelette B.F.F. Fichter K. Ashbourne-Excoffon K.J.D. Sensen C.W. Schere S. Mott S. Denis M. Martindale D. Frohlich J. Morgan K. Koop B. Pimstone S. Kastelein J.J.P. Genest Jr., J. Hayden M.R. Mutations of ABC 1 in Tangier disease and familial high density lipoprotein deficiency.Nat. Genet. 1999; 22: 336-345Google Scholar, 3Bodzioch M. Orso E. Klucken J. Langmann T. Böttcher A. Diederich W. Drobnik W. Barlage S. Büchler C. Porsch-Özcürümez M. Kaminski W.E. Hahmann H.W. Oette K. Rothe G. Aslanidis C. Lackner K.J. Schmitz G. The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease.Nat. Genet. 1999; 22: 347-351Google Scholar, 4Rust S. Rosier M. Funke H. Real J. Amoura Z. Piette J-C. Delueze J-F. Brewer H.B. Duverger N. Denefle P. Assmann G. Tangier disease is caused by mutations in the gene encoding ATP-cassette transporter 1.Nat. Genet. 1999; 22: 352-355Google Scholar, 5Lawn R.M. Wade D.P. Garvin M.R. Wang X. Schwartz K. Porter J.G. Seilhamer J.J. Vaughan A.M. Oram J.F. The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway.J. Clin. Invest. 1999; 104: R25-R31Google Scholar, 6Remaley A.T. Rust S. Rosier M. Knapper C. Naudin L. Broccardo C. Peterson K.M. Koch C. Arnould I. Prades C. Duverger N. Funke H. Assmann G. Dinger M. Dean M. Chimini G. Santamarina-Fojo S. Fredrickson D.S. Denefle P. Brewer Jr., H.B. Human ATP-binding cassette transporter 1 (ABC1): genomic organization and identification of the genetic defect in the original Tangier disease kindred.Proc. Natl. Acad. Sci. USA. 1999; 96: 12685-12690Google the that Tangier cells the removal of both cholesterol and phospholipid by apolipoprotein and the assembly of HDL (7Francis G.A. Knopp R.H. Oram J.F. Defective removal of cellular cholesterol and phospholipids by apolipoprotein A-I in Tangier disease.J. Clin. Invest. 1995; 96: 78-87Google Scholar, 8Remaley A.T. Schumacher U.K. Stonik J.A. Farsi B.D. Nazih H.B. Brewer Jr., H.B. cholesterol transport Tangier disease and of on lipid Scholar, J.F. J. in apolipoprotein-mediated removal of cellular by of human and its by of with Tangier disease Lipid Res. 1999; Scholar, A. A. S. M. Kastelein J.J.P. J. Real G. G. Assmann G. and of Tangier disease patients are in phospholipids apolipoprotein Lipid Res. 1998; Scholar), is that ABC1 is involved in the interaction of the cells and Cholesterol removed by this in the that is by S. of cholesterol incorporation into apolipoprotein-mediated cellular lipid efflux in 1995; Scholar, M. S. by protein of apolipoprotein-mediated cholesterol efflux in Scholar, G.A. Oram J.F. of HDL the of cellular by a mechanism independent of sterol Scholar), the of a cholesterol the ABC1 The that HDL is assembled cholesterol in undifferentiated THP-1 cells on interaction with The HDL was enriched in cholesterol by the PMA treatment of the cells, a in the of HDL that the interaction of apolipoprotein with the cells to generate HDL of the removal of cellular cholesterol by this of in apolipoprotein-mediated HDL assembly was in by of protein in cells S. of cholesterol incorporation into apolipoprotein-mediated cellular lipid efflux in 1995; and M. S. by protein of apolipoprotein-mediated cholesterol efflux in Scholar), and by of cholesterol in differentiated THP-1 cells M.R. A-I cholesterol and apolipoprotein THP-1 Lipid Res. 1999; is that expression of ABC1 with differentiation not parallel the of but was only with cholesterol incorporation into HDL. a ABC1 mutations the removal of cellular phospholipid by (7Francis G.A. Knopp R.H. Oram J.F. Defective removal of cellular cholesterol and phospholipids by apolipoprotein A-I in Tangier disease.J. Clin. Invest. 1995; 96: 78-87Google Scholar, 8Remaley A.T. Schumacher U.K. Stonik J.A. Farsi B.D. Nazih H.B. Brewer Jr., H.B. cholesterol transport Tangier disease and of on lipid Scholar, J.F. J. in apolipoprotein-mediated removal of cellular by of human and its by of with Tangier disease Lipid Res. 1999; Scholar, A. A. S. M. Kastelein J.J.P. J. Real G. G. Assmann G. and of Tangier disease patients are in phospholipids apolipoprotein Lipid Res. 1998; Scholar), that this protein is to involved in the interaction of apolipoprotein with cell The therefore that the low level of ABC1 differentiation is to the apolipoprotein-cell mechanism to this interaction to generate HDL. In the ABC is at the initial low expression and the of cholesterol incorporation into the HDL assembly caused by the level of ABC1 for the apolipoprotein interaction is that for cholesterol of caveolin-1 was also highly induced by PMA in with S. van of and caveolin-1 is with in THP-1 Lipid Res. 1999; This is also with the in cholesterol this protein to function in cholesterol In of this of caveolin-1 expression by antisense DNA to of cholesterol incorporation into HDL assembled by the interaction and resulted in of cholesterol-poor HDL. caveolin-1 was to play independent role in the of cholesterol for the HDL assembly mechanism by apolipoprotein with the cellular lipids. The were with a A. are by cholesterol and by in Natl. Acad. Sci. USA. that the level of caveolin-1 was with cellular cholesterol to with to the in to the cellular cholesterol level and to the by antisense DNA The that the of caveolin-1 in cellular cholesterol is specific to the with apolipoprotein-mediated HDL is to a step to cholesterol at the the assembly of HDL with phospholipid was by the and of caveolin-1 is to the of caveolin-1 in cells, this cell is related to the function of G. M. of and in 1998; that the were out in cells into cholesterol was not ABC1 is not expressed T. Klucken J. M. G. Chimini G. Kaminski W.E. Schmitz G. of the human ATP-binding cassette transporter 1 for in Biophys. Res. 1999; The therefore in Caveolin-1 is to play role in the of cholesterol its function not is in with the of the is identified a K. into 1995; of caveolin-1 is related to cellular cholesterol A. are by cholesterol and by in Natl. Acad. Sci. USA. Scholar, A. Two sterol of gene in to low density lipoprotein Natl. Acad. Sci. USA. Scholar), and its with is by the cholesterol level to the in to cholesterol also that caveolin-1 cholesterol transport the to the role for in transport of cholesterol to by a with a in the A. of a in cholesterol 1998; cholesterol in to involved in the efflux to HDL the efflux of cellular 1995; that both nonspecific and apolipoprotein-mediated that cholesterol by the apolipoprotein-mediated HDL assembly is with in J. S. interaction in and apolipoprotein-mediated cellular cholesterol Lipid Res. 41: In THP-1 cells, of HDL by with and this to the expression of caveolin-1 S. van of and caveolin-1 is with in THP-1 Lipid Res. 1999; The mechanism by caveolin-1 a specific cholesterol to apolipoprotein-mediated HDL assembly is of cholesterol incorporation into HDL by caveolin-1 antisense DNA that this protein is for the the in caveolin-1 expression is a of the in cholesterol incorporation into HDL THP-1 cells are in was with PMA This caused by the of by of H. H. S. S. A. of low density lipoprotein on the cells of human monocytic leukemia cell line Biophys. Res. by in S. van of and caveolin-1 is with in THP-1 Lipid Res. 1999; was the cells were by of in with the that cholesterol are related to the cholesterol enrichment of HDL generated with differentiated cells M.R. A-I cholesterol and apolipoprotein THP-1 Lipid Res. 1999; the the in cellular cholesterol by of undifferentiated cells not cholesterol enrichment of HDL. is not cholesterol is for apolipoprotein-mediated HDL except for the limited of the of the by The in 1 at that the cholesterol not to with PMA In cholesterol into undifferentiated cells not to a in cholesterol incorporation into HDL is with differentiated cells. is that of caveolin-1 expression a of cholesterol enrichment of HDL by PMA-induced cell by cholesterol the to that for apolipoprotein-mediated HDL This in by the of and and the of and ATP-binding cassette transporter 1 apolipoprotein high density lipoprotein low density lipoprotein phorbol 12-myristate 13-acetate