Sterol efflux is impaired from macrophage foam cells selectively enriched with 7-ketocholesterol
Sterol efflux is impaired from macrophage foam cells selectively enriched with 7-ketocholesterol
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DOI：
10.1074/jbc.271.30.17852
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发表时间：
1996-07-26
影响因子：
4.8
通讯作者：
Jessup, W
中科院分区：
文献类型：
--
作者：
Gelissen, IC;Brown, AJ;Jessup, W
本研究的目的是研究先前发现的小鼠腹腔巨噬细胞负载氧化低密度脂蛋白（OxLDL）的胆固醇流出障碍是否可归因于这些细胞中氧化固醇的存在，7-酮胆固醇（7 KC），OxLDL负载细胞中存在的主要氧化固醇，选择性地掺入未氧化的LDL中，随后乙酰化以产生高摄取形式，用富含7 KC的乙酰化LDL（7 kAcLDL）孵育的小鼠巨噬细胞，通过细胞蛋白和台盼蓝排除法判断，未显示细胞毒性。细胞内大部分7 KC被酯化，表明其是酰基CoA：胆固醇酰基转移酶的底物。与装载无氧甾醇乙酰化LDL的细胞相比，装载7 kAcLDL的小鼠巨噬细胞（使用apoA-I作为甾醇受体）的胆固醇流出在含有>50 nmol 7 KC/mg细胞蛋白的细胞中受损，因此，胆固醇流出受损可在装载含有与OxLDL相似比例的7 KC的7 kAcLDL的细胞中再现，7 KC本身输出非常差，即使细胞中7 KC的水平很低。这些结果表明，在体外泡沫细胞中存在的氧固醇可以影响反向固醇转运，并可能是潜在的重要的泡沫细胞形成在体内。
The aim of the present study was to investigate whether impairment of cholesterol efflux previously found from mouse peritoneal macrophages loaded with oxidized low density lipoprotein (OxLDL) could be ascribed to the presence of oxysterols in these cells, 7-Ketocholesterol (7KC), the major oxysterol present in OxLDL-loaded cells, was selectively incorporated into unoxidized LDL, which was subsequently acetylated to produce a high uptake form, Mouse macrophages incubated with 7KC-enriched acetylated LDL (7kAcLDL) did not reveal cytotoxicity judged by cell protein and trypan blue exclusion, A large proportion of cellular 7KC was esterified, indicating that it is a substrate for acyl CoA: cholesterol acyltransferase. Cholesterol efflux from mouse macrophages loaded with 7kAcLDL, using apoA-I as a sterol acceptor, was impaired in cells containing >50 nmol of 7KC/mg of cell protein compared with cells loaded with oxysterol-free acetylated LDL, Thus impairment of cholesterol efflux could be reproduced in cells loaded with 7kAcLDL containing similar proportions of 7KC as OxLDL, 7KC itself was exported very poorly, even when the levels of 7KC in the cells were low. These results suggest that oxysterols present in foam cells in vitro can affect reverse sterol transport and may be potentially important in foam cell formation in vivo.