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Kinetics of cholesterol reverse transport system

胆固醇反向转运系统的动力学

基本信息

批准号：
02044109
负责人：
ICHIKAWA Yoshiyuki
金额：
$ 6.08万
依托单位：
Kagawa Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

项目摘要

The first step of cholesterol reverse transport from peripheral cells to liver is the efflux of cholesterol from the surface of cells by plasma lipoprotein. To clarify the mechanism of the step, we used rat peritoneal macrophage and lipid microemulsion with apolipoprotein A-I. Free cholesterol was released from macrophage when macrophage was incubated with microemulsion and apolipoprotein. Furthermore, cholesterol and phospholipid were released into the incubation medium when it was incubated with only free apolipoprotein. We found that the addition of free apolipoprotein to macrophage caused the formation of discoidal HDL-like particle. The same result was observed using fibroblast and smooth muscle cell but the extent of the efflux of cholesterol from smooth muscle cell was less than that from other cells, The HDL-like particle was quickly disappeared when incubated with lipid microemulsion. Therefore, we concluded that cholesterol efflux from cells to plasma lipoprotein occurred via … More discoidal HDL-like particle.Free cholesterol released from cells is esterified on the surface of HDL and redistributed into plasma lipoproteins. The transfer reaction of lipid between plasma lipoproteins is catalyzed by plasma lipid transfer protein(LTP). We have established the purification of LTP from human plasma. To estimate the accurate transfer rate by LTP, we applied the new method using lipid microemulsion containing fluorescence-labeled lipid (pyrene compound) to the measurement of the transfer rate. The coverage of lipid microemulsion with apolipoprotein was necessary for the lipid transfer by LTP. There was little difference between the transfer rate of cholesteryl ester and triglyceride, however, cholesteryl ester was selectively transferred between microemulsion by LTP when microemulsion contained both cholesteryl ester and triglyceride. The difference of the selectivity of cholesteryl ester over triglyceride was more than a hundred times. Therefore the net movement of cholesteryl ester seemed to occur only between HDL-LDL cholesteryl ester pool and VLDL because there was no net movement of cholesteryl ester between cholesteryl ester-rich particles. Less

胆固醇从外周细胞逆向转运到肝脏的第一步是通过血浆脂蛋白将胆固醇从细胞表面流出。为了阐明这一步骤的机制，我们使用了大鼠腹腔巨噬细胞和载脂蛋白A-I的脂质微乳。巨噬细胞与微乳和载脂蛋白共同孵育后释放出游离胆固醇。此外，胆固醇和磷脂释放到孵育培养基时，它只与游离载脂蛋白孵育。我们发现，在巨噬细胞中加入游离载脂蛋白可引起盘状HDL样颗粒的形成。成纤维细胞和平滑肌细胞也有相同的结果，但平滑肌细胞的胆固醇流出量小于其他细胞。因此，我们得出结论，胆固醇从细胞流出到血浆脂蛋白是通过 ...更多信息从细胞释放的游离胆固醇在HDL表面酯化并重新分布到血浆脂蛋白中。血浆脂质转移蛋白（LTP）催化血浆脂蛋白之间的脂质转移反应。我们已经建立了从人血浆中纯化LTP的方法。为了通过LTP准确估计转移速率，我们将使用含有荧光标记脂质（芘化合物）的脂质微乳液的新方法应用于转移速率的测量。载脂蛋白对脂质微乳的覆盖是LTP转移脂质的必要条件。胆固醇酯和甘油三酯的转移速率差异不大，但当微乳中同时含有胆固醇酯和甘油三酯时，胆固醇酯通过LTP在微乳之间选择性转移。胆固醇酯与甘油三酯的选择性相差上百倍。因此，胆固醇酯的净移动似乎只发生在HDL-LDL胆固醇酯池和VLDL之间，因为富含胆固醇酯的颗粒之间没有胆固醇酯的净移动。少