Molecular and Cellular Physiology of Apolipoprotein A-I Lipidation by the ATP-binding Cassette Transporter A1 (ABCA1)

The dynamics of ABCA1-mediated apoA-I lipidation were investigated in intact human fibroblasts induced with 22(R)-hydroxycholesterol and 9-cis-retinoic acid (stimulated cells). Specific binding parameters of 125I-apoA-I to ABCA1 at 37 °C were determined: Kd = 0.65 μg/ml, Bmax = 0.10 ng/μg cell protein. Lipid-free apoA-I inhibited the binding of 125I-apoA-I to ABCA1 more efficiently than pre-β1-LpA-I, reconstituted HDL particles r(LpA-I), or HDL3 (IC50 = 0.35 ± 1.14, apoA-I; 1.69 ± 1.07, pre-β1-LpA-I; 17.91 ± 1.39, r(LpA-I); and 48.15 ± 1.72 μg/ml, HDL3). Treatment of intact cells with either phosphatidylcholine-specific phospholipase C or sphingomyelinase affected neither 125I-apoA-I binding nor 125I-apoA-I/ABCA1 cross-linking. We next investigated the dynamics of apoA-I lipidation by monitoring the kinetic of apoA-I dissociation from ABCA1. The dissociation of 125I-apoA-I from normal cells at 37 °C was rapid (t½ = 1.4 ± 0.66 h; n = 3) but almost completely inhibited at either 15 or 4 °C. A time course analysis of apoA-I-containing particles released during the dissociation period showed nascent apoA-I-phospholipid complexes that exhibited α-electrophoretic mobility with a particle size ranging from 9 to 20 nm (designated α-LpA-I-like particles), whereas lipid-free apoA-I incubated with ABCA1 mutant (Q597R) cells was unable to form such particles. These results demonstrate that: 1) the physical interaction of apoA-I with ABCA1 does not depend on membrane phosphatidylcholine or sphingomyelin; 2) the association of apoA-I with lipids reduces its ability to interact with ABCA1; and 3) the lipid translocase activity of ABCA1 generates α-LpA-I-like particles. This process plays in vivo a key role in HDL biogenesis. The dynamics of ABCA1-mediated apoA-I lipidation were investigated in intact human fibroblasts induced with 22(R)-hydroxycholesterol and 9-cis-retinoic acid (stimulated cells). Specific binding parameters of 125I-apoA-I to ABCA1 at 37 °C were determined: Kd = 0.65 μg/ml, Bmax = 0.10 ng/μg cell protein. Lipid-free apoA-I inhibited the binding of 125I-apoA-I to ABCA1 more efficiently than pre-β1-LpA-I, reconstituted HDL particles r(LpA-I), or HDL3 (IC50 = 0.35 ± 1.14, apoA-I; 1.69 ± 1.07, pre-β1-LpA-I; 17.91 ± 1.39, r(LpA-I); and 48.15 ± 1.72 μg/ml, HDL3). Treatment of intact cells with either phosphatidylcholine-specific phospholipase C or sphingomyelinase affected neither 125I-apoA-I binding nor 125I-apoA-I/ABCA1 cross-linking. We next investigated the dynamics of apoA-I lipidation by monitoring the kinetic of apoA-I dissociation from ABCA1. The dissociation of 125I-apoA-I from normal cells at 37 °C was rapid (t½ = 1.4 ± 0.66 h; n = 3) but almost completely inhibited at either 15 or 4 °C. A time course analysis of apoA-I-containing particles released during the dissociation period showed nascent apoA-I-phospholipid complexes that exhibited α-electrophoretic mobility with a particle size ranging from 9 to 20 nm (designated α-LpA-I-like particles), whereas lipid-free apoA-I incubated with ABCA1 mutant (Q597R) cells was unable to form such particles. These results demonstrate that: 1) the physical interaction of apoA-I with ABCA1 does not depend on membrane phosphatidylcholine or sphingomyelin; 2) the association of apoA-I with lipids reduces its ability to interact with ABCA1; and 3) the lipid translocase activity of ABCA1 generates α-LpA-I-like particles. This process plays in vivo a key role in HDL biogenesis. Apolipoprotein (apo) 1The abbreviations used are: apo, apolipoprotein; PAGGE, polyacrylamide non-denaturing gradient gel electrophoresis; ABCA1, ATP-binding cassette AI; BSA, bovine serum albumin; CETP, cholesteryl ester transfer protein; FHD, Familial HDL deficiency; HDL, high density lipoprotein; H-TGL, hepatic lipase; LCAT, lecithin: cholesterol acyl transferase; LPC, lysophosphatidylcholine; PC, phosphatidylcholine; PC-PLC, phosphatidylcholine-specific phospholipase C; PE, phosphatidylethanolamine; PI, phosphatidylinositol; r(LpA-I), reconstituted HDL particles; RCT, reverse cholesterol transport; SM-ase, sphingomyelinase; SM, sphingomyelin; SR-BI, scavenger receptor class B type I; TD, Tangier disease; DMEM, Dulbecco's modified Eagle's medium; PBS, phosphate-buffered saline; FC, free cholesterol; PL, phospholipids; TLC, thin layer chromatography. A-I binding to the extracellular domain of ABCA1 results in the activation of apoA-I lipidation, a key step in reverse cholesterol transport (RCT) process, one of the several proposed mechanisms by which HDL may protect against atherosclerotic vascular disease (1Wang N. Tall A.R. Arterioscler. Thromb. Vasc. Biol. 2003; 23: 1178-1184Crossref PubMed Scopus (219) Google Scholar, 2Brewer Jr., H.B. Santamarina-Fojo S. Am. J. Cardiol. 2003; 91: 3E-11EAbstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar, 3Marcil M. Bissonnette R. Vincent J. Krimbou L. Genest J. Circulation. 2003; 107: 1366-1371Crossref PubMed Scopus (35) Google Scholar). The molecular interaction of apoA-I with ABCA1 promotes cholesterol efflux from peripheral cells and macrophages and is critical for the initial formation of HDL particles (1Wang N. Tall A.R. Arterioscler. Thromb. Vasc. Biol. 2003; 23: 1178-1184Crossref PubMed Scopus (219) Google Scholar). The importance of ABCA1 in the lipidation of apoA-I has been strikingly demonstrated by the identification of mutations at the ABCA1 gene locus as the molecular defect of Tangier Disease (TD) and Familial HDL Deficiency (FHD) (4Brooks-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. Loubser O. Ouelette B.F. Fichter K. Ashbourne-Excoffon K.J. Sensen C.W. Scherer S. Mott S. Denis M. Martindale D. Frohlich J. Morgan K. Koop B. Pimstone S. Kastelein J.J. Hayden M.R. Nat. Genet. 1999; 22: 336-345Crossref PubMed Scopus (1509) Google Scholar, 5Marcil 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 (322) Google Scholar). These patients are characterized by extremely low HDL-cholesterol levels, caused by inadequate transport of cellular cholesterol and phospholipids to the extracellular space, leading to hypercatabolism of lipid-poor nascent HDL particles (6Batal R. Tremblay M. Krimbou L. Mamer O. Davignon J. Genest Jr., J. Cohn J.S. Arterioscler. Thromb. Vasc. Biol. 1998; 18: 655-664Crossref PubMed Scopus (63) Google Scholar). ApoA-I has been shown to interact with many proteins including high-density lipoprotein-binding protein (HBP, vigilin), HB2 (7Fidge N.H. J. Lipid Res. 1999; 40: 187-201Abstract Full Text Full Text PDF PubMed Google Scholar), annexin I, annexin VII (8Brownawell A.M. Creutz C.E. Biochemistry. 1996; 35: 6839-6845Crossref PubMed Scopus (26) Google Scholar), fibronectin, collagen I (9Paradis V. A. D. M. Biol. 1996; Google Scholar, A. Google Scholar), and the human of S. C. V. B. R. 2003; PubMed Scopus Google Scholar). the of the is that apoA-I to the scavenger receptor class B type I M. J. PubMed Scopus Google Scholar), which in of cholesteryl but role for in lipid efflux has been several a molecular interaction apoA-I and ABCA1 at the cell J.S. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, O. D. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar), the role of ABCA1 as a apoA-I receptor is a of mechanisms are proposed for is that a interaction apoA-I and ABCA1 on the of J.S. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). A has been proposed interaction apoA-I and lipid in the cell by the translocase activity of ABCA1 O. D. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). by J.A. Santamarina-Fojo S. Brewer Jr., H.B. Res. PubMed Scopus Google Scholar, J.A. Santamarina-Fojo S. Brewer H.B. J. Lipid Res. 2003; Full Text Full Text PDF PubMed Scopus Google shown that a of the class A lipid efflux and to ABCA1. the was to a key for lipid efflux from ABCA1. of binding parameters of apoA-I-containing particles to ABCA1, is not to ABCA1 as a receptor for apoA-I in the of which demonstrate for the protein. A by L. A. J. J. N. Santamarina-Fojo S. Brewer Jr., H.B. J. Lipid Res. 2003; Full Text Full Text PDF PubMed Scopus Google that the hepatic of ABCA1 is of has for apoA-I lipidation in peripheral the were at the by which apoA-I is by ABCA1 and the formation of the affected by apoA-I and HDL by of or by of ABCA1. the dynamics of apoA-I lipidation were investigated by the kinetic parameters of dissociation and the of apoA-I-containing particles during the fibroblasts from normal and with for at the ABCA1 The for the was and by the of the for and were fibroblasts were from of the of patients and and were in Dulbecco's modified Eagle's with and bovine apoA-I was in 4 and against apoA-I was used ApoA-I was with by to a activity of were on and were or not with 22(R)-hydroxycholesterol and 9-cis-retinoic acid for 20 were incubated at 37 °C with 125I-apoA-I in as for in the or of a of to the The cells were with with and with n The of was by and was as by N. C. Tall A.R. J. Biol. Full Text Full Text PDF PubMed Scopus Google with a were to in and or not with 22(R)-hydroxycholesterol and 9-cis-retinoic acid for 20 in were incubated in the or of either of apoA-I or of 125I-apoA-I in for at 37 °C. were on for 15 and with was in and to with of was in were incubated at for h; the was and the cells were with were at 4 °C with 20 and the was to for at 4 °C in of a was with as B. Denis M. Krimbou L. Marcil M. Genest Jr., J. J. Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). either apoA-I or ABCA1 were by or human The of 125I-apoA-I/ABCA1 complexes were by of ApoA-I to were to in and for 20 were incubated at 37 °C for in the or of or to cells were incubated with of 125I-apoA-I in the or of a of were on for 15 and with PBS, and with was as 125I-apoA-I to ABCA1 of were incubated with of human for 20 at 4 by the of protein A to as L. Tremblay M. Davignon J. Cohn J.S. J. Lipid Res. 1998; Full Text Full Text PDF PubMed Google Scholar). The of apoA-I to ABCA1 in the was by ABCA1 mutant (Q597R) was used as a of from were to in and with 22(R)-hydroxycholesterol and 9-cis-retinoic acid for 20 in The cells were incubated for at 37 °C with of 125I-apoA-I in the of binding cells were incubated with a of to of was and the were incubated at 37 15 or 4 °C for the The was cells were in n and the in the and in the cells was by Lipid and Lipid and cholesterol efflux were as M. Bissonnette R. Vincent J. Krimbou L. Genest J. Circulation. 2003; 107: 1366-1371Crossref PubMed Scopus (35) Google with cells were in the cells were with or for cells were for a cells were or not with of 22(R)-hydroxycholesterol and 9-cis-retinoic acid for 20 or cholesterol efflux were at either or with lipid efflux was as in in in the results were as of phospholipids or phospholipids were with as fibroblasts from were to in or and were incubated for with of with The cells were as with lipid-free apoA-I as for of by particles were by as L. Marcil M. Davignon J. Genest Jr., J. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, L. Marcil M. Genest Jr., J. J. Lipid Res. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). were in the to by gel 4 and in the to the by polyacrylamide gradient gel 4 high molecular protein was as a on were 4 particles were by the with with The of 125I-apoA-I or were by of HDL and cholesterol were the A. A. L. J. Biol. Full Text PDF PubMed Google Scholar). of was used in particles were by to lipid-free apoA-I or formation was by analysis with from was from as by PubMed Scopus Google with the is a and on is by low and were to human L. Marcil M. Genest Jr., J. J. Lipid Res. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). were and were by gel and the was gel the were at the of non-denaturing gradient as L. Tremblay M. Davignon J. Cohn J.S. J. Lipid Res. 1998; Full Text Full Text PDF PubMed Google Scholar). of apoA-I-containing by was used as a to which are from the by particles were by to lipid-free apoA-I or The of was by the the binding of 125I-apoA-I to ABCA1 in normal human the binding of 125I-apoA-I to ABCA1, binding were in fibroblasts in which ABCA1 was induced with 22(R)-hydroxycholesterol and 9-cis-retinoic acid (stimulated as as in shown in a and binding of 125I-apoA-I to cells was binding was in This is to of ABCA1 and the of apoA-I binding at the cell We not been to receptor in fibroblasts as with as by gel of cellular by with not The binding and the binding parameters Kd and Bmax for were by the binding for the cells from the from the binding apoA-I to ABCA1 with high = 0.65 ± and the binding was = 0.10 ± ng/μg cell binding of apoA-I to ABCA1 was in than and for the of the not that the binding parameters of 125I-apoA-I/ABCA1 association in the of apoA-I to ABCA1 was shown in apoA-I a with ABCA1. of cells to of cellular ABCA1 and with the and cholesterol efflux were in as shown in to that the association of 125I-apoA-I with ABCA1 was on the cells were incubated with of 125I-apoA-I for at either 37 20 °C or 4 and 125I-apoA-I cell association was as with cells showed ± ± and ± 37 20 °C and 4 are as of the at 37 °C is that the of apoA-I HDL particles is affected by its association with lipid was of to apoA-I particles its interaction with ABCA1. were to the ability of pre-β1-LpA-I, as as reconstituted HDL and HDL particles to for the binding of 125I-apoA-I to ABCA1 in shown in lipid-free apoA-I inhibited the binding of 125I-apoA-I to ABCA1 more efficiently than either pre-β1-LpA-I, reconstituted HDL particles nm of or HDL3 (IC50 = 0.35 ± 1.14, apoA-I; 1.69 ± 1.07, pre-β1-LpA-I; 17.91 ± 1.39, r(LpA-I); and 48.15 ± 1.72 μg/ml, HDL3). were to the in cell binding of the apoA-I may to the 125I-apoA-I binding to particles of the was in which either or HDL3 particles were incubated with 125I-apoA-I used for apoA-I binding and the were by protein of 125I-apoA-I was with or HDL3 not results shown in the of either pre-β1-LpA-I, lipid-free r(LpA-I), or were by and apoA-I was with with as shown in the lipid binding of apoA-I been proposed to in the interaction O. D. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, M. S. A. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar), the was the binding of apoA-I to ABCA1 was on the of lipids at the cell cells were incubated for at 37 °C in the or of either phosphatidylcholine-specific phospholipase C or sphingomyelinase phospholipids were by the cells were with and the lipids by and and than of and of were incubated with of 125I-apoA-I for at 37 °C and 125I-apoA-I binding was as shown in of on the 125I-apoA-I binding was to that the interaction of apoA-I with ABCA1 was not on the of membrane phosphatidylcholine or the of apoA-I to ABCA1 affected by of apoA-I to ABCA1 was as in shown in of intact cells with not 125I-apoA-I to ABCA1. The of a of apoA-I the of 125I-apoA-I to ABCA1 by of ABCA1 mutant (Q597R) that has been shown to not to apoA-I J.S. J. Biol. Full Text Full Text PDF PubMed Scopus Google was used as a for the and showed binding or to ABCA1 A and that the 125I-apoA-I/ABCA1 were by gel shown in 125I-apoA-I/ABCA1 was in to the that with membrane or ABCA1 protein which may apoA-I and in the of on the of 125I-apoA-I to ABCA1 mutant shown in 125I-apoA-I not to mutant with PC-PLC, SM-ase, or We that apoA-I dissociation from ABCA1 with a in apoA-I lipidation the by which apoA-I was by ABCA1, the of the dissociation of apoA-I from ABCA1 were investigated in the time course of the dissociation of 125I-apoA-I from normal cells at 37 °C. The dissociation of 125I-apoA-I from ABCA1 at 37 °C was rapid (t½ = 1.4 ± 0.66 h; n = 125I-apoA-I dissociation from ABCA1 was almost completely inhibited at either 4 or 15 °C that from the cell as intact 125I-apoA-I in the than of the released to the was by the apoA-I dissociation from ABCA1 and cellular cholesterol efflux in cell the of cholesterol efflux in cells was in the of of apoA-I binding shown in cholesterol efflux a to that cholesterol efflux was in cell cholesterol efflux from ABCA1 mutant (Q597R) cells was to the of apoA-I-containing particles by ABCA1 cells from either normal or from (Q597R) in were incubated with of 125I-apoA-I in of for at 37 °C. The was and particles were by shown in apoA-I-containing particles by normal cells exhibited α-electrophoretic mobility with a particle ranging from 9 to 20 a of apoA-I was in the lipid-free apoA-I incubated with mutant cells was unable to form such particles which a molecular and to the lipid-free apoA-I incubated in the cells apoA-I-containing particles released from ABCA1 during the dissociation cells in were incubated with 125I-apoA-I for at 37 °C. to 15 of was and the were incubated at 37 °C for and The was and particles were by shown in 125I-apoA-I incubated for cells a mobility with a molecular of nm apoA-I-containing particles from normal cells at either or exhibited α-electrophoretic mobility with a particle size ranging from 9 to 20 nm (designated α-LpA-I-like the and size of nascent particles are a dissociation We next the α-electrophoretic mobility of particles may caused by were with and incubated with of apoA-I for at 37 °C. apoA-I was by as shown in apoA-I with the of particles We next the of α-LpA-I-like particles. The α-LpA-I-like particles at time was and apoA-I-containing particles were with The phospholipids phosphatidylcholine and were from in on and by of α-LpA-I-like particles SM, ± PC, ± PE, 15 ± LPC, ± and PI, ± The of in α-LpA-I-like particles not at either 1.4 or dissociation period not of the importance of ABCA1 in the of HDL cholesterol (1Wang N. Tall A.R. Arterioscler. Thromb. Vasc. Biol. 2003; 23: 1178-1184Crossref PubMed Scopus (219) Google Scholar, 3Marcil M. Bissonnette R. Vincent J. Krimbou L. Genest J. Circulation. 2003; 107: 1366-1371Crossref PubMed Scopus (35) Google Scholar, L. A. J. J. N. Santamarina-Fojo S. Brewer Jr., H.B. J. Lipid Res. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar), investigated the molecular and mechanisms of apoA-I lipidation in fibroblasts as a for peripheral with by J.A. Santamarina-Fojo S. Brewer Jr., H.B. Res. PubMed Scopus Google Scholar), that binding parameters of 125I-apoA-I to ABCA1 in cells The of 125I-apoA-I binding to ABCA1 was by that apoA-I a with ABCA1 in and was in cells formation was with cellular and cholesterol efflux binding with apoA-I at 4 °C and the results been O. D. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, J. PubMed Scopus Google Scholar). demonstrate that the apoA-I cell association showed that apoA-I binding to ABCA1 may by process the in may the lipid in the which apoA-I cell This the importance of to the the of apoA-I HDL particles and its interaction with ABCA1, that showed that pre-β1-LpA-I, reconstituted HDL particles r(LpA-I), and HDL3 particles are for the binding of 125I-apoA-I to ABCA1 with lipid-free apoA-I This role for the association of apoA-I with lipids in pre-β1-LpA-I, which apoA-I with a of phospholipids J. Lipid Res. Full Text PDF PubMed Google a to interact with ABCA1 to lipid-free apoA-I that the lipid of as as the of apoA-I particles from of HDL PubMed Scopus Google Scholar, J. Lipid Res. Full Text PDF PubMed Google Scholar). is proposed to initial of cholesterol J. Lipid Res. Full Text PDF PubMed Google Scholar). This the that cellular lipid by process than The of the interaction to been molecular ABCA1 and apoA-I J.S. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, O. D. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, J.A. Santamarina-Fojo S. Brewer Jr., H.B. Res. PubMed Scopus Google Scholar), is a apoA-I and ABCA1. been proposed for 1) V. M. Biochemistry. 1999; PubMed Scopus Google that phospholipids in the extracellular of macrophages as initial for to ABCA1; 2) O. D. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google that ABCA1 the of membrane its association with cellular that are with apoA-I binding to membrane lipids than membrane protein. the been to and was in that of to demonstrate that of intact cells with or affected neither the binding of 125I-apoA-I nor A and is that are to a which is not on the of membrane phosphatidylcholine or is not that membrane phospholipids or the phospholipase lipid may to the of apoA-I to ABCA1. This is with a by C. A. J. Biol. Full Text Full Text PDF PubMed Scopus Google that ABCA1 is with in cell the cellular association of apoA-I is not by annexin a binding protein. J. Biol. Full Text Full Text PDF PubMed Scopus Google that cholesterol and membrane not lipid for efflux by the ABCA1-mediated lipid has been that the of ABCA1 to by the of ABCA1 or its lipid activity O. D. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, N. C. Tall A.R. J. Biol. Full Text Full Text PDF PubMed Scopus Google was for apoA-I from and shown that ABCA1 by plays role in the apoA-I lipidation B. Denis M. Krimbou L. Marcil M. Genest Jr., J. J. Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar, B. N. Tall A.R. J. Biol. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar, S. A. J. R. V. Zhang L.H. M. Hayden M.R. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar), that lipidation of apoA-I by ABCA1 is We and by that 125I-apoA-I dissociation from ABCA1 was almost completely inhibited at either 4 or 15 °C The of apoA-I lipidation by ABCA1 not been in to process in apoA-I lipidation in a by monitoring the kinetic parameters of apoA-I dissociation from ABCA1. We that apoA-I dissociation from ABCA1 with a in apoA-I lipidation with the that the transfer of and cholesterol from the of ABCA1 to apoA-I the interaction of and dissociation of the apoA-I is by the that: 1) apoA-I dissociation from ABCA1 is rapid 2) the association of apoA-I with lipids reduces its ability to interact with ABCA1; 3) the lipid translocase activity of ABCA1 generates α-LpA-I-like particles; and ABCA1 not of apoA-I in has been shown to cholesterol efflux in macrophages S. A. 1999; PubMed Scopus Google Scholar), the that ABCA1 may in the and of apoA-I in are to a role of ABCA1 in the of apoA-I in fibroblasts and of the dissociation of apoA-I from ABCA1 and cholesterol efflux showed for the time that apoA-I dissociation from ABCA1 is rapid (t½ = 1.4 in cell cholesterol efflux a demonstrated that lipid-free cellular and during of J. Lipid Res. Full Text PDF PubMed Google Scholar, S. J. Biol. Full Text PDF PubMed Google Scholar), such as S. J. Lipid Res. 1998; Full Text Full Text PDF PubMed Google in a time that in the fibroblasts were not with ABCA1 was not induced and the cells were with a high of and results that ABCA1 at the cell may lipidation which may in the lipidation of many apoA-I by the ABCA1 This is by by Tall and B. N. Tall A.R. J. Biol. 2003; Full Text Full Text PDF PubMed Scopus Google that in the of the ABCA1 and leading to of ABCA1 cell and demonstrated that apoA-I incubated with cells including fibroblasts J. Lipid Res. Full Text PDF PubMed Google Scholar), cells R. M.R. J. Lipid Res. Full Text PDF PubMed Google Scholar), and macrophages S. J. Biol. Full Text PDF PubMed Google was to and cholesterol from the cells to form in that the complexes during apoA-I with normal cells a of particles with molecular lipid-free apoA-I was unable to form particles during its with mutant The particles was a time course analysis of apoA-I-containing particles from ABCA1 showed nascent apoA-I-phospholipid complexes that exhibited α-electrophoretic mobility with a particle size ranging from 9 to 20 nm (designated α-LpA-I-like The of the molecular and of nascent particles a dissociation period not the of a the particles and for is to that the α-LpA-I-like particles that particles phospholipids and cholesterol whereas the particles phospholipids and apoA-I B. Zhang L. Arterioscler. Thromb. Vasc. Biol. PubMed Scopus Google Scholar). of the of cholesterol activity in the extracellular to to cholesteryl is that α-LpA-I-like particles are was that a with a high of a high and α-electrophoretic mobility S. J. Biol. Full Text PDF PubMed Google Scholar), with that α-LpA-I-like particles a high in ± the of a by L. M. S. J. Biol. 2003; Full Text Full Text PDF PubMed Scopus Google that of apoA-I with macrophages to the formation of more than one type of apoA-I-containing particles with a molecular of the that is a of and to apoA-I a membrane is to results with in that which demonstrated that apoA-I-containing particles a size and of apoA-I in its lipid-free is that the cell used in the lipidation of used human fibroblasts and L. M. S. J. Biol. 2003; Full Text Full Text PDF PubMed Scopus Google used cells were with and were with 22(R)-hydroxycholesterol and 9-cis-retinoic acid and cells were with and induced with that the and of the particles are from of lipid-free apoA-I and We that on the analysis of particles released during the dissociation period critical for the of by a lipid translocase activity of ABCA1. has been that lipid-free apoA-I is to interact efficiently with ABCA1 in that lipid which are not in in B.F. Arterioscler. Thromb. Vasc. Biol. PubMed Scopus Google Scholar), a role in We that lipid-free apoA-I during apoA-I-containing particles A. R. B. J. C. B. J. Biol. Full Text PDF PubMed Google are by ABCA1 and form α-LpA-I-like particles may in results the We demonstrate that of 125I-apoA-I was from ABCA1 at (t½ the the of apoA-I-containing particles during the dissociation period was shown to with phospholipids α-electrophoretic mobility This is by by Arterioscler. Thromb. Vasc. Biol. 22: PubMed Scopus Google that the mobility of 125I-apoA-I from to α-electrophoretic mobility the that hepatic has the to the size of HDL, in with the of A. R. B. J. C. B. J. Biol. Full Text PDF PubMed Google Scholar). kinetic proposed to the of cell a in peripheral and many lipid-free with apoA-I for ABCA1 results that apoA-I binding to ABCA1 was to in a and association as a interaction or a interaction in the the lipid translocase activity of ABCA1 lipid-free apoA-I to α-LpA-I-like ABCA1 to as the lipidation of the that than either or The that the interaction of lipid-free apoA-I with ABCA1 generates α-LpA-I-like particles to lipid-free apoA-I is in in human the of lipid-free apoA-I by the of hepatic on and a of in process K. A. Brewer Jr., H.B. Santamarina-Fojo S. J. Lipid Res. 1999; 40: Full Text Full Text PDF PubMed Google Scholar), lipid-free apoA-I by ABCA1 and α-LpA-I-like particles The results in a for a cellular apoA-I lipidation that ABCA1 protein in peripheral This process plays in vivo a key role in the of nascent HDL particles.

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