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J Biol Chem, Vol. 273, Issue 20, 12140-12147, May 15, 1998
From the 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.
Selective Uptake of Low Density Lipoprotein-Cholesteryl Ester Is
Enhanced by Inducible Apolipoprotein E Expression in Cultured Mouse
Adrenocortical Cells
,,
Department of Pharmacological Sciences,
University Medical Center, State University of New York, Stony
Brook, New York 11794, ¶ Geriatric Research, Education and
Clinical Center, Department of Veterans Affairs Palo Alto Heath
Care System, Palo Alto, California 94304, and the
§ Department of Basic Science and Oral Research, University
of Colorado, Denver, Colorado 80262
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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