title: Scavenger receptor B1 (SR-B1) profoundly excludes high density lipoprotein (HDL) apolipoprotein AII as it nibbles HDL-cholesteryl ester.
abstract: 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-[3H]CE labeled with [125I]apoAI or [125I]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 (2-4×) than apoAI. To distinguish gobblingversusnibbling 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.
authors.affiliation: From the Houston Methodist Research Institute, Houston Texas 77030, bgillard@houstonmethodist.org.|Weill Cornell Medicine, New York, New York 10065, and.
authors.forename: Baiba K
authors.identifier: 0000-0002-2527-5102
authors.initials: BK
authors.lastname: Gillard
authors.affiliation: the Baylor College of Medicine, Houston, Texas 77030.
authors.forename: G Randall
authors.initials: GR
authors.lastname: Bassett
authors.affiliation: From the Houston Methodist Research Institute, Houston Texas 77030.|Weill Cornell Medicine, New York, New York 10065, and.
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Gotto
authors.affiliation: From the Houston Methodist Research Institute, Houston Texas 77030.|Weill Cornell Medicine, New York, New York 10065, and.
authors.forename: Corina
authors.initials: C
authors.lastname: Rosales
authors.affiliation: From the Houston Methodist Research Institute, Houston Texas 77030.|Weill Cornell Medicine, New York, New York 10065, and.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Pownall
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism; D016633:Apolipoprotein A-II / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D002788:Cholesterol Esters / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics / Q000378:metabolism*; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D002788:Cholesterol Esters; C059714:HDL cholesteryl ester; D008075:Lipoproteins, HDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B
keywords: apolipoprotein; apolipoprotein AII; atherosclerosis; cholesterol; high-density lipoprotein (HDL); lipid; reverse cholesterol transport; scavenger receptor; scavenger receptor B1; selective lipid uptake