Selective uptake of cholesteryl esters from various classes of lipoproteins by HepG2 cells

Selective uptake of cholesteryl eaters (CE) from lipoproteins by cells has been extensively studied with high density lipoproteins (HDL). It is only r ecently that such a mechanism has been attributed to intermediate and low d ensity lipoproteins (IDL and LDL). Here, we compare the association of prot eins and CE from very low density lipoproteins (VLDL), IDL, LDL and HDL3 to HepG2 cells. These lipoproteins were either labelled in proteins with I-12 5 or in CE with H-cholesteryl oleate. We show that, at any lipoprotein conc entration, protein association to the cells is significantly smaller for ID L, LDL, and HDL3 than CE association, but not for VLDL. At a concentration of 20 mu g lipoprotein/mL, these associations reveal CE-selective uptake in the order of 2-, 4-, and 11-fold for IDL, LDL, and HDL3, respectively. The se studies reveal that LDL and HDL3 are good selective donors of CE to HepG 2 cells, while LDL is a poor donor and VLDL is not a donor. A significant i nverse correlation (r(2) = 0.973) was found between the total lipid/protein ratios of the four classes of lipoproteins and the extent of CE-selective uptake by HepG2 cells. The fate of H-3-CE of the two best CE donors (LDL an d HDL3) was followed in HepG2 cells after 3 h of incubation. Cells were sho wn to hydrolyze approximately 25% of the H-3-CE of both lipoproteins. Howev er, when the cells were treated with 100 mu M of chloroquine, a lysosomotro yic agent, 85 and 40% of H-3-CE hydrolysis was lost for LDL and HDL3, respe ctively. The fate of LDL and HDL3-CE in HepG2 cells deficient in LDL-recept or was found to be the same, indicating that the portion of CE hydrolysis s ensitive to chloroquine is not significantly linked to LDL-receptor activit y. Thus, in HepG2 cells, the magnitude of CE-selective uptake is inversely correlated with the total lipid/protein ratios of the lipoproteins and CE-s elective uptake from the two best CE donors (LDL and HDL3) appears to follo w different pathways.