This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 27/8/1828    most recent ATVBAHA.107.142455v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mulya, A. Articles by Parks, J. S. Search for Related Content PubMed PubMed Citation Articles by Mulya, A. Articles by Parks, J. S.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1828.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Minimal Lipidation of Pre-ß HDL by ABCA1 Results in Reduced Ability to Interact with ABCA1

Anny Mulya; Ji-Young Lee; Abraham K. Gebre; Michael J. Thomas; Perry L. Colvin; John S. Parks

From the Departments of Pathology/Section on Lipid Sciences (A.M., J.-Y.L., A.K.G., J.S.P.) and Biochemistry (M.J.T.), Wake Forest University Health Sciences, Winston-Salem, NC; the Division of Gerontology (P.L.C.), University of Maryland School of Medicine, and the Department of Veterans Affairs and Veterans Affairs Medical Center Baltimore (P.L.C.), Geriatric Research, Education and Clinical Center (GRECC), Md. Current address for J.-Y.L.: Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, Nebr.

Correspondence to John S. Parks, PhD, Department of Pathology/Section on Lipid Sciences, Wake Forest University Health Sciences, Medical Center Blvd., Winston-Salem, NC 27157-1040. E-mail jparks{at}wfubmc.edu

Objectives— The aim of this study was to determine the role of ATP binding cassette transporter A1 (ABCA1) on generation of different-sized nascent HDLs.

Methods and Results— HEK293 cells stably-transfected with ABCA1 (HEK293-ABCA1) or non-transfected (control) cells were incubated with lipid free ¹²⁵I-apoA-I for 24 hours. Incubation of apoA-I with HEK293-ABCA1 cells, but not control cells, led to the formation of heterogeneous-sized, pre-ß migrating nascent HDL subpopulations (pre-ß1 to -4) that varied in size (7.1 to 15.7 nm), lipid, and apoA-I content. Kinetic studies suggested that all subpopulations were formed simultaneously, with no evidence for a precursor-product relationship between smaller and larger-sized particles. When isolated nascent pre-ß HDLs (pre-ß1 to -4) were added back to HEK293-ABCA1 cells, their ability to bind to ABCA1 and efflux lipid was severely compromised. Heat-denaturation of pre-ß1 HDL resulted in partial recovery of ABCA1 binding, suggesting that initial interaction of apoA-I with ABCA1 results in a constrained conformation of apoA-I that decreases subsequent binding.

Conclusions— Interaction of apoA-I with ABCA1 results in the simultaneous generation of pre-ß HDLs of discrete size and chemical composition. These nascent particles are poor substrates for subsequent lipidation by ABCA1 and presumably require additional non-ABCA1-mediated lipidation for further maturation.

Incubation of apoA-I with ABCA1-expressing cells generated heterogeneous-sized nascent pre-ß HDLs, which appear to form simultaneously. These particles are poor substrates for ABCA1, suggesting that the initial interaction of apoA-I with ABCA1 results in a constrained conformation of apoA-I and that further maturation of these nascent HDL occurs via non–ABCA1-mediated pathways.

Key Words: ATP binding cassette transporter A1 • apolipoprotein AI • high density lipoprotein

This article has been cited by other articles:

				K. Nagao, Y. Zhao, K. Takahashi, Y. Kimura, and K. Ueda Sodium taurocholate-dependent lipid efflux by ABCA1: effects of W590S mutation on lipid translocation and apolipoprotein A-I dissociation J. Lipid Res., June 1, 2009; 50(6): 1165 - 1172. [Abstract] [Full Text] [PDF]

				A. Mulya, J.-Y. Lee, A. K. Gebre, E. Y. Boudyguina, S.-K. Chung, T. L. Smith, P. L. Colvin, X.-C. Jiang, and J. S. Parks Initial interaction of apoA-I with ABCA1 impacts in vivo metabolic fate of nascent HDL J. Lipid Res., November 1, 2008; 49(11): 2390 - 2401. [Abstract] [Full Text] [PDF]

				D.-Q. Peng, G. Brubaker, Z. Wu, L. Zheng, B. Willard, M. Kinter, S. L. Hazen, and J. D. Smith Apolipoprotein A-I Tryptophan Substitution Leads to Resistance to Myeloperoxidase-Mediated Loss of Function Arterioscler. Thromb. Vasc. Biol., November 1, 2008; 28(11): 2063 - 2070. [Abstract] [Full Text] [PDF]

				J. P. Mauldin, M. H. Nagelin, A. J. Wojcik, S. Srinivasan, M. D. Skaflen, C. R. Ayers, C. A. McNamara, and C. C. Hedrick Reduced Expression of ATP-Binding Cassette Transporter G1 Increases Cholesterol Accumulation in Macrophages of Patients With Type 2 Diabetes Mellitus Circulation, May 27, 2008; 117(21): 2785 - 2792. [Abstract] [Full Text] [PDF]

				I. Zanotti, F. Poti, M. Pedrelli, E. Favari, E. Moleri, G. Franceschini, L. Calabresi, and F. Bernini The LXR agonist T0901317 promotes the reverse cholesterol transport from macrophages by increasing plasma efflux potential J. Lipid Res., May 1, 2008; 49(5): 954 - 960. [Abstract] [Full Text] [PDF]

				P. T. Duong, G. L. Weibel, S. Lund-Katz, G. H. Rothblat, and M. C. Phillips Characterization and properties of pre{beta}-HDL particles formed by ABCA1-mediated cellular lipid efflux to apoA-I J. Lipid Res., May 1, 2008; 49(5): 1006 - 1014. [Abstract] [Full Text] [PDF]