Uptake of apolipoprotein E-rich and apolipoprotein E-poor subfractions of high-density lipoprotein by liver membranes and HepG2 cells.
Apolipoprotein (apo) E plays an important role in mediating high-density lipoprotein (HDL) cholesterol transport and uptake by the liver. Evidence for and against the existence of conventional liver receptors for HDL containing apoE have been reported, although the selective uptake of the cholesterol moiety of HDL has been demonstrated. The present study investigated the hepatic uptake of subfractions of HDL separated on the basis of their apoE content. Rabbit HDL and its apoE-rich and apoE-poor subfractions, separated by heparin-Sepharose affinity chromatography, were labelled in their apoprotein moieties with [14C]sucrose and in their cholesteryl ester moiety with 3H. No binding of either subfraction to rabbit liver membranes could be detected. With cultured HepG2 cells, however, there was a high uptake of 3H but a very low uptake of 14C from both HDL subfractions, demonstrating that selective uptake was operating. Addition of unlabelled apoE-poor HDL inhibited the uptake of both labels from the two subfractions to the same extent. These studies, which differed from previously reported investigations by employing native homologous HDL subfractions of known apolipoprotein composition, demonstrated that apoE is not directly involved in the selective uptake of HDL cholesterol by the liver. In the absence of specific binding sites on liver membranes, it is suggested that an alternative mechanism might exist for the clearance of HDL cholesterol from the plasma.
D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D002846:Chromatography, Affinity; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D011817:Rabbits; D012685:Sepharose / Q000031:analogs & derivatives
D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C037405:heparin-sepharose; D012685:Sepharose