title: Nascent HDL formation in hepatocytes and role of ABCA1, ABCG1, and SR-BI.
abstract: To study the mechanisms of hepatic HDL formation, we investigated the roles of ABCA1, ABCG1, and SR-BI in nascent HDL formation in primary hepatocytes isolated from mice deficient in ABCA1, ABCG1, or SR-BI and from wild-type (WT) mice. Under basal conditions, in WT hepatocytes, cholesterol efflux to exogenous apoA-I was accompanied by conversion of apoA-I to HDL-sized particles. LXR activation by T0901317 markedly enhanced the formation of larger HDL-sized particles as well as cellular cholesterol efflux to apoA-I. Glyburide treatment completely abolished the formation of 7.4 nm diameter and greater particles but led to the formation of novel 7.2 nm-sized particles. However, cells lacking ABCA1 failed to form such particles. ABCG1-deficient cells showed similar capacity to efflux cholesterol to apoA-I and to form nascent HDL particles compared with WT cells. Cholesterol efflux to apoA-I and nascent HDL formation were slightly but significantly enhanced in SR-BI-deficient cells compared with WT cells under basal but not LXR activated conditions. As in WT but not in ABCA1-deficient hepatocytes, 7.2 nm-sized particles generated by glyburide treatment were also detected in ABCG1-deficient and SR-BI-deficient hepatocytes. Our data indicate that hepatic nascent HDL formation is highly dependent on ABCA1 but not on ABCG1 or SR-BI.
authors.affiliation: Departments of Internal Medicine, University of Kentucky, Lexington, KY; Cardiovascular Research Center, University of Kentucky, Lexington, KY; Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY.
authors.forename: Ailing
authors.initials: A
authors.lastname: Ji
authors.affiliation: Departments of Internal Medicine, University of Kentucky, Lexington, KY; Cardiovascular Research Center, University of Kentucky, Lexington, KY; Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Wroblewski
authors.affiliation: Departments of Internal Medicine, University of Kentucky, Lexington, KY; Cardiovascular Research Center, University of Kentucky, Lexington, KY; Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY.
authors.forename: Lei
authors.initials: L
authors.lastname: Cai
authors.affiliation: Physiology, University of Kentucky, Lexington, KY; Cardiovascular Research Center, University of Kentucky, Lexington, KY; Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY.
authors.forename: Maria C
authors.initials: MC
authors.lastname: de Beer
authors.affiliation: Departments of Internal Medicine, University of Kentucky, Lexington, KY; Cardiovascular Research Center, University of Kentucky, Lexington, KY; Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY.
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Webb
authors.affiliation: Departments of Internal Medicine, University of Kentucky, Lexington, KY; Cardiovascular Research Center, University of Kentucky, Lexington, KY; Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY; Molecular and Cellular Biochemistry and Physiology, University of Kentucky, Lexington, KY; Department of Veterans Affairs Medical Center, Lexington, KY. Electronic address: dvwest1@uky.edu.
authors.forename: Deneys R
authors.initials: DR
authors.lastname: van der Westhuyzen
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*
chemical_list: C577836:ABCA1 protein, human; C487540:ABCG1 protein, mouse; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D008074:Lipoproteins; D008075:Lipoproteins, HDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002784:Cholesterol