ABCA1 mediates concurrent cholesterol and phospholipid efflux to apolipoprotein A-I

• Main Authors: Jonathan D. Smith, Wilfried Le Goff, Megan Settle, Gregory Brubaker, Christine Waelde, Andrew Horwitz, Michael N. Oda
• Format: Article
• Language: English
• Published: Elsevier 2004-04-01
• Series: Journal of Lipid Research
• Subjects: lipid efflux; ATP binding cassette transporter A1; Tangier disease; reverse cholesterol transport; endocytosis; cyclodextrin
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520318472

Prior studies provide data supporting the notion that ATP binding cassette transporter A1 (ABCA1) promotes lipid efflux to extracellular acceptors in a two-step process: first, ABCA1 mediates phospholipid efflux to an apolipoprotein, and second, this apolipoprotein-phospholipid complex accepts free cholesterol in an ABCA1-independent manner. In the current study using RAW264.7 cells, ABCA1-mediated free cholesterol and phospholipid efflux to apolipoprotein A-I (apoA-I) were tightly coupled to each other both temporally and after treatment with ABCA1 inhibitors. The time course and temperature dependence of ABCA1-mediated lipid efflux to apoA-I support a role for endocytosis in this process. Cyclodextrin treatment of RAW264.7 cells partially inhibited 8Br-cAMP-induced efflux of free cholesterol and phospholipid to apoA-I.ABCA1-expressing cells are more sensitive to cell damage by high-dose cyclodextrin and vanadate, leading to increased lactate dehydrogenase leakage and phospholipid release even in the absence of the acceptor apoA-I. Finally, we could not reproduce a two-step effect on lipid efflux using conditioned medium from ABCA1-expressing cells pretreated with cyclodextrin.