Characterization and properties of preβ-HDL particles formed by ABCA1-mediated cellular lipid efflux to apoA-I*

Journal of Lipid Research

Sissel Lund-Katz¹  George H. Rothblat¹  Ginny L. Weibel¹  Phu T. Duong¹  Michael C. Phillips¹ 

[1] Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4318;

关键词: phospholipids;    cholesterol;    lipoprotein;    reverse cholesterol transport;    fibroblasts;    high density lipoprotein;   

DOI  :  

来源: DOAJ

【 摘 要 】

The contribution of ABCA1-mediated efflux of cellular phospholipid (PL) and cholesterol to human apolipoprotein A-I (apoA-I) to the formation of preβ1-HDL (or lipid-poor apoA-I) is not well defined. To explore this issue, we characterized the nascent HDL particles formed when lipid-free apoA-I was incubated with fibroblasts in which expression of the ABCA1 was upregulated. After a 2 h incubation, the extracellular medium contained small apoA-I/PL particles (preβ1-HDL; diameter = 7.5 ± 0.4 nm). The preβ1-HDL (or lipid-poor apoA-I) particles contained a single apoA-I molecule and three to four PL molecules and one to two cholesterol molecules. An apoA-I variant lacking the C-terminal α-helix did not form such particles when incubated with the cell, indicating that this helix is critical for the formation of lipid-poor apoA-I particles. These preβ1-HDL particles were as effective as lipid-free apoA-I molecules in mediating both the efflux of cellular lipids via ABCA1 and the formation of larger, discoidal HDL particles. In conclusion, preβ1-HDL is both a product and a substrate in the ABCA1-mediated reaction to efflux cellular PL and cholesterol to apoA-I. A monomeric apoA-I molecule associated with three to four PL molecules (i.e., lipid-poor apoA-I) has similar properties to the lipid-free apoA-I molecule.

【 授权许可】

Unknown