The low density lipoprotein receptor-related protein contributes to selective uptake of high density lipoprotein cholesteryl esters by SW872 liposarcoma cells and primary human adipocytes
The low density lipoprotein receptor-related protein contributes to selective uptake of high density lipoprotein cholesteryl esters by SW872 liposarcoma cells and primary human adipocytes
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DOI：
10.1074/jbc.m103954200
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发表时间：
2001-12-28
影响因子：
4.8
通讯作者：
McPherson, R
中科院分区：
文献类型：
--
作者：
Vassiliou, G;Benoist, F;McPherson, R
高密度脂蛋白（HDL）衍生的胆固醇酯（CE）的选择性转移不需要脂蛋白内化的概念最近受到了挑战，有证据表明，在选择性摄取过程中HDL再循环。这促使我们研究低密度脂蛋白受体相关蛋白（LRP）在选择性摄取中的作用。LRP是能够介导选择性摄取的脂蛋白脂酶（LpL）和载脂蛋白E（apoE）配体的内吞受体。我们报道了干扰配体与LRP结合的分子，如受体相关蛋白（RAP）、苏拉明、α（2）-巨球蛋白或乳铁蛋白，可抑制人原代脂肪细胞和SW 872脂肪肉瘤细胞对HDL-CE的选择性摄取35- 50%。这种对总HDL选择性摄取的部分抑制并不是由于对HDL 3或HDL 3亚组分的优先抑制。清除剂受体BI的选择性摄取不受RAP的抑制，排除其参与。此外，在SW 872细胞中，LRP通过稳定的反义表达降低至对照水平的14%，选择性摄取减弱至少33%，证实了LRP在此过程中的作用。RAP、α（2）-巨球蛋白、乳铁蛋白和苏拉明（单独或成对组合）也使原代人脂肪细胞对HDL-CE的选择性摄取减弱约40%。另一方面，人皮肤成纤维细胞大量表达LRP，但缺乏选择性摄取的能力，表明需要其他分子。在SW 872细胞中，外源性apoE或LpL可以促进选择性摄取，但只有apoE增强的摄取可以被RA-P抑制，暗示apoE可能是一种辅助介质。我们讨论了内吞受体LRP介导选择性摄取的可能机制。
The concept that selective transfer of high density lipoprotein (HDL)-derived cholesteryl esters (CE) does not require lipoprotein internalization has been challenged recently by evidence that implicates HDL recycling during the selective uptake process. This has prompted us to examine the role of the low density lipoprotein receptor-related protein (LRP) in selective uptake. LRP is an endocytic receptor for lipoprotein lipase (LpL) and apolipoprotein E (apoE) ligands that are able to mediate selective uptake. We report that molecules that interfere with ligand binding to LRP, such as the receptor-associated protein (RAP), suramin, alpha(2)-macroglobulin, or lactoferrin, inhibit HDL-CE selective uptake by human primary adipocytes and SW872 liposarcoma cells by 35-50%. This partial inhibition of selective uptake from total HDL was not due to preferential inhibition of the HDL3 or HDL3 subfractions. Selective uptake by the scavenger receptor BI was not inhibited by RAP, excluding its involvement. Furthermore, in SW872 cells in which LRP was reduced to 14% of control levels by stable antisense expression, selective uptake was attenuated by at least 33%, confirming a role for LRP in this process. RAP, alpha(2)-macroglobulin, lactoferrin, and suramin (individually or in paired combinations) also attenuated selective uptake of HDL-CE by primary human adipocytes by about 40%. On the other hand, human skin fibroblasts express LRP abundantly but lack the capacity for selective uptake, demonstrating that other molecules are required. In SW872 cells, exogenous apoE or LpL can facilitate selective uptake but only the apoE-enhanced uptake can be inhibited by RA-P, implicating apoE as a likely co-mediator. We discuss the possible mechanisms by which the endocytic receptor, LRP, can mediate selective uptake.