Selective uptake of low density lipoprotein-cholesteryl ester is enhanced by inducible apolipoprotein E expression in...

Apolipoprotein (apo) E is expressed at high levels by steroidogenic cells of the adrenal gland, ovary, and testis. The cell surface location of apoE in adrenocortical cells suggests that apoE may facilitate the uptake of lipoprotein cholesterol by either the endocytic or the selective uptake pathways, or both. To examine these possibilities, the human apoE gene was expressed in murine Y1 adrenocortical cells under control of an inducible tetracycline-regulated promoter. The results show that induction of apoE yielded a 2-2.5-fold increase in the uptake of low density lipoprotein-cholesteryl ester (LDL-CE) but had little effect on high density lipoprotein-CE uptake. Analysis of lipoprotein uptake pathways showed that apoE increased LDL-CE uptake by both endocytic and selective uptake pathways. In terms of cholesterol delivery to the adrenal cell, the apoE-mediated enhancement of LDL-CE selective uptake was quantitatively more important. Furthermore, the predominant effect of apoE expression was on the low affinity component of LDL-CE selective uptake. LDL particles incubated with apoE-expressing cells contained 0.92 +/- 0.11 apoE molecules/apoB after gel filtration chromatography, indicating stable complex formation between apoE and LDL. ApoE expression by Y1 cells was necessary for enhanced LDL-CE selective uptake. This result may indicate an interaction between apoE-containing LDL and cell surface apoE. These data suggest that apoE produced locally by steroidogenic cells facilitates cholesterol acquisition by the LDL selective uptake pathway.