Uptake and fate of class B scavenger receptor ligands in HepG2 cells

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Abstract
Class B scavenger receptors (SR‐Bs) interact with native, acetylated and oxidized low‐density lipoprotein (LDL, AcLDL and OxLDL), high‐density lipoprotein (HDL3) and maleylated BSA (M‐BSA). The aim of this study was to analyze the catabolism of CD36‐ and LIMPII‐analogous‐1 (CLA‐1), the human orthologue for the scavenger receptor class B type I (SR‐BI), and CD36 ligands in HepG2 (human hepatoma) cells. Saturation binding experiments revealed moderate‐affinity binding sites for all the SR‐B ligands tested with dissociation constants ranging from 20 to 30 µg·mL−1. Competition binding studies at 4 °C showed that HDL and modified and native LDL share common binding site(s), as OxLDL competed for the binding of 125I‐LDL and 125I‐HDL3 and vice versa, and that only M‐BSA and LDL may have distinct binding sites. Degradation/association ratios for SR‐B ligands show that LDL is very efficiently degraded, while M‐BSA and HDL3 are poorly degraded. The modified LDL degradation/association ratio is equivalent to 60% of the LDL degradation ratio, but is three times higher than that of HDL3. All lipoproteins were good cholesteryl ester (CE) donors to HepG2 cells, as a 3.6–4.7‐fold CE‐selective uptake ([3H]CE association/125I‐protein association) was measured. M‐BSA efficiently competed for the CE‐selective uptake of LDL‐, OxLDL‐, AcLDL‐ and HDL3‐CE. All other lipoproteins tested were also good competitors with some minor variations. Hydrolysis of [3H]CE‐lipoproteins in the presence of chloroquine demonstrated that modified and native LDL‐CE were mainly hydrolyzed in lysosomes, whereas HDL3‐CE was hydrolyzed in both lysosomal and extralysosomal compartments. Inhibition of the selective uptake of CE from HDL and native modified LDL by SR‐B ligands clearly suggests that CLA‐1 and/or CD36 are involved at least partially in this process in HepG2 cells.

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