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J Biol Chem, Vol. 274, Issue 42, 29733-29739, October 15, 1999
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From the Scavenger receptor, class B, type I (SR-BI) is a
cell-surface glycoprotein that mediates selective uptake of high
density lipoprotein cholesteryl ester (CE) without the concomitant
uptake and degradation of the particle. We have investigated the
endocytic and selective uptake of low density lipoprotein (LDL)-CE by
SR-BI using COS-7 cells transiently transfected with mouse SR-BI.
Analysis of lipoprotein uptake data showed a
concentration-dependent LDL-CE-selective uptake when doubly
labeled LDL particles were incubated with SR-BI-expressing COS-7 cells.
In contrast to vector-transfected cells, SR-BI-expressing COS-7 cells
showed marked increases in LDL cell association and CE uptake by the
selective uptake pathway, but only a modest increase in CE uptake by
the endocytic pathway. SR-BI-mediated LDL-CE-selective uptake exceeded
LDL endocytic uptake by 50-100-fold. SR-BI-mediated LDL-CE-selective
uptake was not inhibited by the proteoglycan synthesis inhibitor,
p-nitrophenyl- Department of Pharmacological Sciences,
University Medical Center, State University of New York,
Stony Brook, New York 11794 and § Geriatric Research,
Education and Clinical Center, Veteran Affairs Palo Alto Health
Care System, Palo Alto, California 94304
-D-xylopyranoside or by the sulfation inhibitor sodium chlorate, indicating that SR-BI-mediated LDL-CE uptake occurs independently of LDL interaction with cell-surface proteoglycan. Analyses with subclones of Y1 adrenocortical cells showed
that LDL-CE-selective uptake was proportional to the level of SR-BI
expression. Furthermore, antibody directed to the extracellular domain
of SR-BI blocked LDL-CE-selective uptake in adrenocortical cells. Thus,
in cells that normally express SR-BI and in transfected COS-7 cells
SR-BI mediates the efficient uptake of LDL-CE via the selective uptake
mechanism. These results suggest that SR-BI may influence the
metabolism of apoB-containing lipoproteins in vivo by
mediating LDL-CE uptake into SR-BI-expressing cells.
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