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  • Title: Expression of caveolin-1 in hepatic cells increases oxidized LDL uptake and preserves the expression of lipoprotein receptors.
    Author: Truong TQ, Brodeur MR, Falstrault L, Rhainds D, Brissette L.
    Journal: J Cell Biochem; 2009 Nov 01; 108(4):906-15. PubMed ID: 19718657.
    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.
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