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J Biol Chem, Vol. 274, Issue 47, 33398-33402, November 19, 1999
From the The clearance of free cholesterol from plasma
lipoproteins by tissues is of major quantitative importance, but it is
not known whether this is passive or receptor-mediated. Based on our
finding that scavenger receptor BI (SR-BI) promotes free cholesterol
(FC) exchange between high density lipoprotein (HDL) and cells, we tested whether SR-BI would effect FC movement in vivo using
[14C]FC- and [3H]cholesteryl ester
(CE)-labeled HDL in mice with increased (SR-BI transgenic (Tg)) or
decreased (SR-BI attenuated (att)) hepatic SR-BI expression. The
initial clearance of HDL FC was increased in SR-BI Tg mice by 72% and
decreased in SR-BI att mice by 53%, but was unchanged in apoA-I
knockout mice compared with wild-type mice. Transfer of FC to non-HDL
and esterification of FC were minor and could not explain differences.
The hepatic uptake of FC was increased in SR-BI Tg mice by 34% and
decreased in SR-BI att mice by 22%. CE clearance and uptake gave
similar results, but with much slower rates. The uptake of HDL FC and
CE by SR-BI Tg primary hepatocytes was increased by 2.2- and 2.6-fold
(1-h incubation), respectively, compared with control hepatocytes. In
SR-BI Tg mice, the initial biliary secretion of [14C]FC
was markedly increased, whereas increased [3H]FC appeared
after a slight delay. Thus, in the mouse, a major portion of the
clearance of HDL FC from plasma is mediated by SR-BI.
Hepatic Scavenger Receptor BI Promotes Rapid Clearance of High
Density Lipoprotein Free Cholesterol and Its Transport into Bile
,,
,
Division of Molecular Medicine, Millennium Pharmaceuticals, Inc.,
Cambridge, Massachusetts 02139
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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