期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 292, 期 21, 页码 8864-8873出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M117.781963
关键词
apolipoprotein; atherosclerosis; cholesterol; high-density lipoprotein (HDL); lipid; scavenger receptor; apolipoprotein AII; reverse cholesterol transport; scavenger receptor B1; selective lipid uptake
资金
- National Institutes of Health [HL-56865, HL-129767]
- Bass Foundation
- Houston Methodist Foundation
Reverse cholesterol transport (transfer of macrophage-cholesterol in the subendothelial space of the arterial wall to the liver) is terminated by selective high density lipoprotein (HDL)-cholesteryl ester (CE) uptake, mediated by scavenger receptor class B, type 1 (SR-B1). We tested the validity of two models for this process: gobbling, i.e. one-step transfer of all HDL-CE to the cell and nibbling, multiple successive cycles of SR-B1-HDL association during which a few CEs transfer to the cell. Concurrently, we compared cellular uptake of apoAI with that of apoAII, which is more lipophilic than apoAI, using HDL-[H-3]CE labeled with [I-125]apoAI or [I-125]apoAII. The studies were conducted in CHO-K1 and CHO-ldlA7 cells (LDLR-/-) with (CHO-SR-B1) and without SR-B1 overexpression and in human Huh7 hepatocytes. Relative to CE, both apoAI and apoAII were excluded from uptake by all cells. However, apoAII was more highly excluded from uptake (2-4x) than apoAI. To distinguish gobbling versus nibbling mechanisms, media from incubations of HDL with CHO-SR-B1 cells were analyzed by non-denaturing PAGE, size-exclusion chromatography, and the distribution of apoAI, apoAII, cholesterol, and phospholipid among HDL species as a function of incubation time. HDL size gradually decreased, i.e. nibbling, with the concurrent release of lipid-free apoAI; apoAII was retained in an HDL remnant. Our data support an SR-B1 nibbling mechanism that is similar to that of streptococcal serum opacity factor, which also selectively removes CE and releases apoAI, leaving an apoAII-rich remnant.
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