title: Expression of caveolin-1 in hepatic cells increases oxidized LDL uptake and preserves the expression of lipoprotein receptors.
abstract: Oxidized LDL (OxLDL) that are positively associated with the risk of developing cardiovascular diseases are ligands of scavenger receptor-class B type I (SR-BI) and cluster of differentiation-36 (CD36) which can be found in caveolae. The contribution of these receptors in human hepatic cell is however unknown. The HepG2 cell, a human hepatic parenchymal cell model, expresses these receptors and is characterized by a very low level of caveolin-1. Our aim was to define the contribution of human CD36, SR-BI, and caveolin-1 in the metabolism of OxLDL in HepG2 cells and conversely the effects of OxLDL on the levels/localization of these receptors. By comparing mildly (M)- and heavily (H)-OxLDL metabolism between control HepG2 cells and HepG2 cells overexpressing CD36, SR-BI, or caveolin-1, we found that (1) CD36 increases M- and H-OxLDL-protein uptake; (2) SR-BI drives M-OxLDL through a degradation pathway at the expense of the cholesterol ester (CE) selective uptake pathway; (3) caveolin-1 increases M- and H-OxLDL-protein uptake and decreases CE selective uptake from M-OxLDL. Also, incubation with M- or H-OxLDL decreases the levels of SR-BI and LDL-receptor in control HepG2 cells which can be overcome by caveolin-1 expression. In addition, OxLDL move CD36 from low to high buoyant density membrane fractions, as well as caveolin-1 in cells overexpressing this protein. Thus, hepatic caveolin-1 expression has significant effects on OxLDL metabolism and on lipoprotein receptor levels.
authors.affiliation: Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec, Canada H3C 3P8.
authors.forename: To Quyen
authors.initials: TQ
authors.lastname: Truong
authors.forename: Mathieu R
authors.initials: MR
authors.lastname: Brodeur
authors.forename: Louise
authors.initials: L
authors.lastname: Falstrault
authors.forename: David
authors.initials: D
authors.lastname: Rhainds
authors.forename: Louise
authors.initials: L
authors.lastname: Brissette
mesh_terms: D001692:Biological Transport; D018955:CD36 Antigens / Q000096:biosynthesis / Q000378:metabolism; D051242:Caveolin 1 / Q000096:biosynthesis*; D002460:Cell Line; D002470:Cell Survival; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008099:Liver / Q000166:cytology* / Q000378:metabolism*; D008954:Models, Biological; D011973:Receptors, LDL / Q000378:metabolism*
chemical_list: D018955:CD36 Antigens; D051242:Caveolin 1; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; C099252:oxidized low density lipoprotein