Molecular mechanism of reverse cholesterol transport:: Reaction of pre-β-migrating high-density lipoprotein with plasma lecithin/cholesterol acyltransferase

被引:55
作者
Nakamura, Y
Kotite, L
Gan, Y
Spencer, TA
Fielding, CJ
Fielding, PE [1 ]
机构
[1] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[3] Daiichi Pure Chem, Tokyo, Japan
[4] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA
[5] Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA
关键词
D O I
10.1021/bi0485629
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A 70-75 kDa high-density lipoprotein (HDL) particle with pre-beta-electrophoretic migration (pre-beta(1)-HDL) has been identified in several studies as an early acceptor of cell-derived cholesterol. However, the further metabolism of this complex has not been determined. Here we sought to identify the mechanism by which cell-derived cholesterol was esterified and converted to mature HDL as part of reverse cholesterol transport (RCT). Human plasma selectively immunodepleted of pre-beta(1)-HDL was used to study factors regulating pre-beta(1)-HDL production. A major role for phospholipid transfer protein (PLTP) in the recycling of pre-beta(1)-HDL was identified. Cholesterol binding, esterification by lecithin/cholesterol acyltransferase (LCAT) and transfer by cholesteryl ester transfer protein (CETP) were measured using H-3-cholesterol-labeled cell monolayers. LCAT bound to H-3-free cholesterol (FC)-labeled pre-beta(1)-HDL generated cholesteryl esters at a rate much greater than the rest of HDL. The cholesteryl ester produced in pre-beta(1)-HDL in turn became the preferred substrate of CETP. Selective LCAT-mediated reactivity with pre-beta(1)-HDL represents a novel mechanism increasing the efficiency of RCT.
引用
收藏
页码:14811 / 14820
页数:10
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