Human ABCA7 Supports Apolipoprotein-mediated Release of Cellular Cholesterol and Phospholipid to Generate High Density Lipoprotein

Abstract

Apolipoprotein-mediated release of cellular cholesterol and phospholipids was induced in HEK293 cells by expressing human ATP-binding cassette transporter A7 (ABCA7) and ABC transporter A1 (ABCA1) proteins, whether transient or stable, to generate cholesterol-rich high density lipoprotein (HDL). Green fluorescent protein (GFP) attached at their C termini did not influence the lipid release reactions. Transfected ABCA7-GFP induced apolipoprotein-mediated assembly of cholesterol-containing HDL also in L929 cells, which otherwise generate only cholesterol-deficient HDL with their endogenous ABCA1. Time-dependent release of cholesterol and phospholipid by apolipoprotein A (apoA)-I was parallel both with ABCA1 and with ABCA7 when highly expressed in HEK293 cells, but dose-dependent profiles of lipid release on apoA-I and apoA-II were somewhat different between ABCA1 and ABCA7. Analyses of the stable clones with ABCA1-GFP (293/2c) and ABCA7-GFP (293/6c) by using the same vector indicated some differences in regulation of their activities by protein kinase modulators. Dibutyryl cyclic AMP increased ABCA1-GFP and the release of cholesterol and phospholipid in 293/2c but increased neither ABCA7-GFP nor the lipid release in 293/6c. Expression of ABCA1-GFP- and apoA-I-mediated lipid release were enhanced in parallel by phorbol 12-myristate 13-acetate (PMA) in 293/2c cells. In contrast, the same treatment of 293/6c increased ABCA7-GFP, but apoA-I-mediated lipid release was significantly suppressed. Despite these different responses to PMA, all of the effects of PMA were reversed by a specific protein kinase C inhibitor Gö6976, suggesting that the changes were in fact due to protein kinase C activation. A thiol protease inhibitor, N-acetyl-Leu-Leu-norleucinal, increased the protein levels of ABCA1-GFP in 293/2c and ABCA7-GFP in 293/6c, indicating their common degradation pathway. The data indicated that human ABCA7 would compensate the function of ABCA1 for release of cell cholesterol in a certain condition(s), but post-transcriptional regulation of their activity is different. Apolipoprotein-mediated release of cellular cholesterol and phospholipids was induced in HEK293 cells by expressing human ATP-binding cassette transporter A7 (ABCA7) and ABC transporter A1 (ABCA1) proteins, whether transient or stable, to generate cholesterol-rich high density lipoprotein (HDL). Green fluorescent protein (GFP) attached at their C termini did not influence the lipid release reactions. Transfected ABCA7-GFP induced apolipoprotein-mediated assembly of cholesterol-containing HDL also in L929 cells, which otherwise generate only cholesterol-deficient HDL with their endogenous ABCA1. Time-dependent release of cholesterol and phospholipid by apolipoprotein A (apoA)-I was parallel both with ABCA1 and with ABCA7 when highly expressed in HEK293 cells, but dose-dependent profiles of lipid release on apoA-I and apoA-II were somewhat different between ABCA1 and ABCA7. Analyses of the stable clones with ABCA1-GFP (293/2c) and ABCA7-GFP (293/6c) by using the same vector indicated some differences in regulation of their activities by protein kinase modulators. Dibutyryl cyclic AMP increased ABCA1-GFP and the release of cholesterol and phospholipid in 293/2c but increased neither ABCA7-GFP nor the lipid release in 293/6c. Expression of ABCA1-GFP- and apoA-I-mediated lipid release were enhanced in parallel by phorbol 12-myristate 13-acetate (PMA) in 293/2c cells. In contrast, the same treatment of 293/6c increased ABCA7-GFP, but apoA-I-mediated lipid release was significantly suppressed. Despite these different responses to PMA, all of the effects of PMA were reversed by a specific protein kinase C inhibitor Gö6976, suggesting that the changes were in fact due to protein kinase C activation. A thiol protease inhibitor, N-acetyl-Leu-Leu-norleucinal, increased the protein levels of ABCA1-GFP in 293/2c and ABCA7-GFP in 293/6c, indicating their common degradation pathway. The data indicated that human ABCA7 would compensate the function of ABCA1 for release of cell cholesterol in a certain condition(s), but post-transcriptional regulation of their activity is different. Cholesterol is essential for all animal cells as a membrane constituent for regulation of its general physicochemical properties and functions of specific domains. Cellular cholesterol can be derived by de novo synthesis or externally supplied via the uptake of cholesterol-containing lipoprotein particles. In contrast, most of the cells are unable to catabolize cholesterol so that cholesterol molecules must be removed from the cells and transported to the liver for their conversion to bile acids as a major exit route of the body cholesterol. Thus cholesterol transport from the peripheral cells to the liver is an essential part of cholesterol homeostasis, both for cells and for the body. High density lipoprotein (HDL) 1The abbreviations used are: HDL, high density lipoprotein; ABC, ATP-binding cassette; ABCA1, ABC transporter A1; ABCG1, ABC transporter G1; ABCA7, ABC transporter A7; GFP, green fluorescent protein; DF, Dulbecco's modified Eagle's medium and Ham's F12 medium; FCS, fetal calf serum; apoA, apolipoprotein A; BSA, bovine serum albumin; lysoPC, lysophosphatidylcholine; dBcAMP, dibutyryl cyclic AMP; PMA, phorbol 12-myristate 13-acetate; ALLN, N-acetyl-Leu-Leu-norleucinal; PKC, protein kinase C; PKA, cAMP-dependent protein kinase. 1The abbreviations used are: HDL, high density lipoprotein; ABC, ATP-binding cassette; ABCA1, ABC transporter A1; ABCG1, ABC transporter G1; ABCA7, ABC transporter A7; GFP, green fluorescent protein; DF, Dulbecco's modified Eagle's medium and Ham's F12 medium; FCS, fetal calf serum; apoA, apolipoprotein A; BSA, bovine serum albumin; lysoPC, lysophosphatidylcholine; dBcAMP, dibutyryl cyclic AMP; PMA, phorbol 12-myristate 13-acetate; ALLN, N-acetyl-Leu-Leu-norleucinal; PKC, protein kinase C; PKA, cAMP-dependent protein kinase. is believed to play a central role in this pathway. Lipid-free apolipoproteins with amphiphilic α-helical segments were demonstrated to remove cellular lipids to generate cholesterol-containing HDL (1.Hara H. Yokoyama S. J. Biol. Chem. 1991; 266: 3080-3086Abstract Full Text PDF PubMed Google Scholar, 2.Yokoyama S. Biochim. Biophys. Acta. 2000; 1529: 231-244Crossref PubMed Scopus (117) Google Scholar). This reaction was shown deficient in fibroblasts from patients with familial HDL deficiency, Tangier disease (3.Francis G.A. Knopp R.H. Oram J.F. J. Clin. Invest. 1995; 96: 78-87Crossref PubMed Scopus (369) Google Scholar, 4.Remaley A.T. Schumacher U.K. Stonik J.A. Farsi B.D. Nazih H.B. Brewer H.B.J. Arterioscler. Thromb. Vasc. Biol. 1997; 17: 1813-1821Crossref PubMed Scopus (190) Google Scholar), and therefore found essential for generation of plasma HDL. Mutations were identified in one of the members of ATP-binding cassette (ABC) transporter superfamily, ABC transporter A1 (ABCA1), as the cause of Tangier disease and other genetic HDL deficiencies (5.Bodzioch 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. Nat. Genet. 1999; 22: 347-351Crossref PubMed Scopus (1328) Google Scholar, 6.Brooks-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. Scherer 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. Nat. Genet. 1999; 22: 336-345Crossref PubMed Scopus (1481) Google Scholar, 7.Marcil M. Brooks-Wilson A. Clee S.M. Roomp K. Zhang L.H. Yu L. Collins J.A. van Dam M. Molhuizen H.O. Loubster O. Ouellette B.F. Sensen C.W. Fichter K. Mott S. Denis M. Boucher B. Pimstone S. Genest Jr., J. Kastelein J.J. Hayden M.R. Lancet. 1999; 354: 1341-1346Abstract Full Text Full Text PDF PubMed Scopus (315) Google Scholar, 8.Remaley 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. Assman G. Dinger M. Dean M. G. S. Brewer H.B. S. A. 1999; 96: PubMed Scopus Google Scholar, S. Rosier M. Funke H. J. Brewer H.B. Duverger N. G. Nat. Genet. 1999; 22: PubMed Scopus Google so that a role of this protein in the generation of HDL by the of the HDL ABC transporter an ABC transporter protein of a also to the apolipoprotein A lipid release from J. Büchler C. E. Kaminski W.E. Porsch-Özcürümez M. G. M. Diederich W. Drobnik W. Dean M. Schmitz G. S. A. 2000; PubMed Scopus Google Scholar). is whether this protein can generate HDL in the of ABCA1. ABC transporter A7 (ABCA7) is of the same of transporter as ABCA1, and its from the human and high to other human ABC W.E. A. Schmitz G. Biophys. 2000; PubMed Scopus Google Scholar). ABCA7 also identified as the an of which was found to the of ABCA1 S. K. A. S. T. N. T. Yokoyama S. K. Biophys. PubMed Scopus Google Scholar). ABCA7 and protein were induced in from human peripheral and was expressed to the cellular cholesterol W.E. A. Schmitz G. Biophys. 2000; PubMed Scopus Google Scholar). an role of ABCA7 in cellular cholesterol is play a role in regulation of cholesterol in some specific cells as was that ABCA7 apoA-I-mediated phospholipid release but to release cholesterol N. D. M. W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). that human ABCA7 generation of HDL by both cellular cholesterol and phospholipid in the of ABCA1. the reaction is to that of human ABCA1, of apolipoproteins for the cells is different. of its and activity by protein kinase are also different from of ABCA1. and for human ABCA1 and ABCA7 were as S. K. A. S. T. N. T. Yokoyama S. K. Biophys. PubMed Scopus Google Scholar). were to and to for the or with green fluorescent protein (GFP) at their C the an of for of HEK293 and L929 cells were from and in of Dulbecco's modified Eagle's medium and Ham's F12 medium with of fetal calf serum a of at were with to the to which the were were with and clones with high of the were to the fluorescent with of was with an K. S. I. K. Yokoyama S. Biochim. Biophys. Acta. PubMed Scopus Google Scholar, Yokoyama S. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), a and an to the levels of the generate the the of human ABCA7, acids was expressed as a protein with at the C in by and K. and used for Expression levels of ABCA1-GFP protein and ABCA7-GFP protein were also in with an fluorescent Cellular was as fluorescent derived was by of protein was by their by using an with a and apoA-II were from human plasma HDL and at as S. S. A. J. PubMed Scopus Google Scholar, S. Yokoyama S. A. J. Biol. Chem. Full Text PDF PubMed Google Scholar). were and at as S. S. H. Yokoyama S. 2000; PubMed Scopus Google Scholar). Cellular were in at a density of with a the cells were with and and in of medium bovine serum and lipid and with acids was used of medium in some to the endogenous in in the medium and cells was the indicated for lipid and for cholesterol and were S. S. H. Yokoyama S. 2000; PubMed Scopus Google Scholar). in with and T. K. Clin. PubMed Scopus Google was also to the of a for in were in at a density of as and with of medium and apoA-I for from was and to remove cell and of the was for density (1.Hara H. Yokoyama S. J. Biol. Chem. 1991; 266: 3080-3086Abstract Full Text PDF PubMed Google Scholar). The was from the The of cholesterol and as as the density were for were by of by A was as HEK293 cells did not to apolipoproteins to release cholesterol or phospholipid with dibutyryl cyclic AMP and phorbol 12-myristate 13-acetate (PMA) with or to apoA-I and data not of ABCA1 and ABCA7 in HEK293 cells in apoA-I-mediated release of both cholesterol and phospholipid in a dose-dependent and of to the C of ABCA7 or ABCA1 did not influence these lipid of the functions of ABCA7, therefore stable clones expressing high levels of ABCA1-GFP protein and ABCA7-GFP lipid release from HEK293 cells with protein kinase in a of cholesterol and phospholipid by with apoA-I was demonstrated at in clones highly expressing ABCA1-GFP and also clones expressing ABCA7-GFP, indicating that the reaction is not but data of HEK293 cells, the cells with or transient of ABCA1 and ABCA7, and (293/2c) and (293/6c) are shown in ABCA1 nor ABCA7 protein was in HEK293 cells. and were at the with of molecules in 293/2c and 293/6c cells, as ABCA1-GFP and ABCA7-GFP at and ABCA1 protein cell protein in 293/2c cells was as of that in human and L929 by not protein was between 293/2c and 293/6c cells on and of and the that ABCA1-GFP S. T. G. K. M. N. T. M. Yokoyama S. K. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google and ABCA7-GFP were in plasma as was in cells expressing ABCA7 M. A. S. A. Biophys. PubMed Scopus Google and in HEK293 cells expressing ABCA7 N. D. M. W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google of dBcAMP, PMA and on apoA-I-mediated lipid release and ABCA1-GFP protein in 293/2c cells. 293/2c cells were for as for The cells were with in or with and was a for lipid cells were with and was the and for of the lipid release and for of cellular GFP, and and and and with and the of dBcAMP, PMA and on apoA-I-mediated lipid release and ABCA7-GFP protein in 293/6c cells. 293/6c cells were in the same as in the and for are same as in profiles of lipid release by apoA-I and apoA-II from 293/2c and 293/6c cells are shown in that most of the to the medium in the of apolipoproteins was and that its was of apolipoprotein not The dose-dependent of the reaction by apoA-II was to that of apoA-I with to of the for both cholesterol and indicated that ABCA7 both cholesterol and phospholipid to as ABCA1 The of phospholipid and cholesterol parallel by of apoA-I and apoA-II in 293/2c and 293/6c The lipid release to the at of apolipoprotein with the cells (293/2c) the cells The for the release of cholesterol and phospholipid from 293/6c cells was and and and and for that from 293/2c cells and data not of apoA-I-mediated lipid release the of release of phospholipid and cholesterol both from 293/2c cells and from 293/6c cells as cholesterol and phospholipid in the medium were as as apoA-I and increased for of the medium demonstrated that both cholesterol and phospholipid were in the with a density at indicating that HDL were from the cells to the cells and in apoA-I-mediated release of cholesterol and from 293/2c and 293/6c cells. 293/2c and and 293/6c and cells were for as in with cells were in the cholesterol and and and in the medium was shown are from of of the data is from a for 293/2c and from for of lipids from 293/2c and 293/6c cells. were and with was as Expression of ABCA7-GFP also induced cholesterol release in L929 cells. that L929 cells release phospholipid but not cholesterol by apoA-I S. Yokoyama S. Biochim. Biophys. Acta. PubMed Scopus Google Scholar). shown in L929 cells only phospholipid to apoA-I at high of apoA-I of ABCA7-GFP protein in L929 cells release of cholesterol with of phospholipid release The of endogenous ABCA1 was not in L929 by and of ABCA7 and PMA enhanced apoA-I-mediated lipid release and ABCA1-GFP protein in In the of or PMA with was induced in cholesterol and phospholipid release from 293/2c cells A and The of the lipid release was with of ABCA1-GFP protein by and and The effects of and PMA were not in the demonstrated of ABCA1 by apolipoprotein thiol degradation Yokoyama S. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, S. Yokoyama S. Biochim. Biophys. Acta. PubMed Scopus Google Scholar, N. W. B. J. Clin. Invest. PubMed Scopus Google Scholar, M. S. Yokoyama S. J. Biol. Chem. 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A thiol protease inhibitor, enhanced apoA-I-mediated lipid release and ABCA1-GFP protein as as the of in 293/2c and In contrast, treatment with did not apoA-I-mediated cholesterol or phospholipid release in 293/6c cells, and PMA release of both lipids A and the other apoA-I and the of ABCA7-GFP in 293/6c, the in cholesterol and phospholipid release was not A and ABCA7-GFP protein was not significantly by dBcAMP, was by PMA and of the cholesterol release to from 293/2c or 293/6c not effects of dBcAMP, PMA, and apoA-I were in HEK293 cells or expressing ABCA7 and data not of ABCA1 and ABCA7 by or PMA was in 293/2c and 293/6c cells, by their In 293/2c cells, PMA induced the transient of ABCA1-GFP as the was a at was at to a of The of these were of cellular in the medium not with these the apoA-I-mediated lipid release from 293/2c for was not by but was enhanced by PMA not In 293/6c cells, was neither by nor by PMA levels were increased in parallel with lipid release in 293/2c cells when with ALLN, the was and in 293/6c not Gö6976, a inhibitor G. H. G. H. D. C. J. Biol. Chem. Full Text PDF PubMed Google Scholar), reversed all of the changes by In 293/2c cells, the of apoA-I-mediated lipid release and ABCA1-GFP was and In 293/6c cells, of the apoA-I-mediated lipid release by PMA was and the ABCA7-GFP was to the and effects on apoA-I-mediated lipid release from 293/2c or 293/6c The function and its regulation of human ABCA7 was by using its expressing of in HEK293 cells. ABCA7 a function for generation of cholesterol-containing HDL the with apoA-I and apoA-II so as human ABCA1 of ABCA7 to protein kinase and PMA, was somewhat different from ABCA1. ABCA1 protein was increased by and its function for the apoA-I-mediated lipid release was increased in ABCA7 and its activity were not increased by ABCA7 was increased by PMA, but its activity for lipid release by apolipoprotein was suppressed. of the effects of PMA were reversed by inhibitor Gö6976, indicating that are by of ABCA1 of plasma HDL, as demonstrated in the patients with Tangier disease (5.Bodzioch 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. Nat. Genet. 1999; 22: 347-351Crossref PubMed Scopus (1328) Google Scholar, 6.Brooks-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. Scherer S. Mott S. Denis M. Martindale D. Frohlich J. Morgan K. Koop B. Pimstone S. Kastelein J.J.P. Genest Jr., J. 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A. 2000; PubMed Scopus Google Scholar), to that is for of plasma HDL. the cellular function as a of lipid transport in its in function is not of with the and of the release of cholesterol and ABCA1 was not J. Büchler C. E. Kaminski W.E. Porsch-Özcürümez M. G. M. Diederich W. Drobnik W. Dean M. Schmitz G. S. A. 2000; PubMed Scopus Google Scholar). was also shown that levels of in from patients with Tangier disease were significantly the function of was not S. M. C. B. M. J. J. Biophys. PubMed Scopus Google Scholar). demonstrated that human ABCA7 the cellular lipid release and assembly of HDL in a as human ABCA1 in the to the of ABCA7 in the of ABCA1 so that this is an function of this at in The from L929 cells expressing ABCA7-GFP in to their endogenous ABCA1 that the effects of ABCA1 and ABCA7 in apolipoprotein-mediated HDL generation be is not whether ABCA1 and ABCA7 generate HDL cholesterol-deficient and cholesterol-containing in this The reaction of ABCA1 and be their and In HEK293 cells, release of lipid at a of apoA-I and apoA-II when ABCA1 was expressed in the cells expressing ABCA7 at and The with ABCA1 were with with ABCA1 was induced by dBcAMP, as shown by that the was increased ABCA7 was and not S. S. H. Yokoyama S. 2000; PubMed Scopus Google Scholar). A dose-dependent was with human cells in which ABCA1 was found S. Yokoyama S. Biochim. Biophys. Acta. PubMed Scopus Google but not ABCA7 not is for the for this in profiles of the HDL assembly between ABCA1 and ABCA7. HEK293 cells expressing ABCA7 phospholipids but not cholesterol by in the of or of cholesterol N. D. M. W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). HEK293 cells expressing ABCA1 were to generate cholesterol-containing HDL N. D. M. W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, N. C. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), the be between human ABCA7 and ABCA7. The of on ABCA1-GFP in 293/2c is with the an of ABCA1 in human fibroblasts S. Yokoyama S. Biochim. Biophys. Acta. PubMed Scopus Google Scholar), cells S. S. H. Yokoyama S. 2000; PubMed Scopus Google Scholar, M. M. C. E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), and J. M. and D. J. Biol. Chem. by that is a in the ABCA1 S. Peterson K. Knapper C. L. J.F. J. A. C. Prades C. G. E. T. Duverger N. Rosier M. 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A indicated that by at a specific of ABCA1 is but for the apoA-I-mediated phospholipid release R.H. S. A. J. Zhang L.H. M. G. Hayden M.R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). with the cellular to A. M. B. G. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google or fibroblasts B. Denis M. L. Marcil M. Genest J. J. Full Text Full Text PDF PubMed Scopus Google Scholar). of ABCA7 by be different in this The of the PMA, also the of ABCA1 and ABCA7. ABCA1-GFP in 293/2c was increased by PMA, and the activity also increased in parallel In contrast, PMA the apoA-I-mediated lipid release from 293/6c expressing ABCA7-GFP A and did not cause of the and effects of PMA were all reversed by Gö6976, an inhibitor of of G. H. G. H. D. C. J. Biol. Chem. Full Text PDF PubMed Google Scholar). The data that specific activities of ABCA7 can be by of ABC not that degradation of ABCA1 is by apolipoproteins from the degradation by thiol most Yokoyama S. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, M. S. Yokoyama S. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). was to ABCA1 protein expressed in HEK293 cells, indicating that ABCA1 protein expressed by the is by the with other N. W. B. J. Clin. Invest. PubMed Scopus Google Scholar, M. S. Yokoyama S. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The with the ABCA7 were to with ABCA1, that the of these are The of the activity of ABCA7 in this be ABCA1 is A. M. B. G. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar), and its in the of plasma HDL (5.Bodzioch 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. Nat. Genet. 1999; 22: 347-351Crossref PubMed Scopus (1328) Google Scholar, 6.Brooks-Wilson A. Marcil M. Clee S.M. Zhang L.-H. Roomp K. van Dam M. Yu L. 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Genet. 1999; 22: PubMed Scopus Google Scholar), of ABCA7 is to in human W.E. A. Schmitz G. Biophys. 2000; PubMed Scopus Google and C. J. Prades C. S. Arnould I. Naudin L. C. Rosier M. B. Dean M. G. Genet. PubMed Scopus Google or in in M. A. S. A. Biophys. PubMed Scopus Google and N. D. M. W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the lipid release not significantly to a of plasma HDL. play an role in cellular cholesterol in In Tangier of is found in in the fibroblasts of the cells, and cells G. A. Brewer H.B. D. The and of Scholar). is to that Tangier disease patients to be only at increased the of plasma HDL and cholesterol in of G. A. Brewer H.B. D. The and of Scholar). ABCA1 of lipid to Tangier disease and in in K. S. Peterson J. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). that is a the of in the of ABCA1, and the lipid release from in the is one of the In ABCA7 protein is in peripheral in by W.E. A. Schmitz G. Biophys. 2000; PubMed Scopus Google Scholar). of this protein be in of the by which ABCA7 the release of cholesterol and generation of HDL with for and of cholesterol by with ABCA1. would also to for treatment of of ABCA7 in certain specific or cells, as and cells, would be to remove cholesterol from peripheral to by or in with ABCA1. for and at for for are also to for of and of to the of the