Cellular cholesterol efflux. Role of cell membrane kinetic pools and interaction with apolipoproteins AI, AII, and Cs.
Cellular cholesterol efflux. Role of cell membrane kinetic pools and interaction with apolipoproteins AI, AII, and Cs.
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DOI：
10.1016/s0021-9258(18)42867-0
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发表时间：
1992-03
期刊：
影响因子：
--
通讯作者：
F. Mahlberg;G. Rothblat
中科院分区：
文献类型：
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作者：
F. Mahlberg;G. Rothblat
在卵磷脂酰胆碱盘状复合物和纯化载脂蛋白（含apoAI、AII或Cs）存在的情况下，监测各种细胞中[14C]胆固醇的外排。当供体细胞为J774巨噬细胞时，含有apoAI的颗粒比含有apoAI或Cs的颗粒更有效。当相同的受体制剂暴露于Fu5AH大鼠肝癌或兔主动脉平滑肌细胞时，未观察到差异。载脂蛋白在刺激J774细胞去除胆固醇方面的差异效率在从同一细胞分离的质膜富集部分中得到维持。从暴露于载脂蛋白ai复合物的J774细胞中获得的动力学数据的非线性回归分析表明，胆固醇外排最符合描述两个动力学室释放的曲线。大约10%的胆固醇从t1/2为1.5至3小时的快速交换池中转移，其余部分从t1/2约为20小时的较慢池中释放。通过改变受体的浓度或载脂蛋白组成来调节J774细胞的胆固醇外排影响池的大小和慢池的t1/2。从J774细胞分离的膜中流出胆固醇的动力学也最适合双室模型，受体载脂蛋白组成的修饰诱导了池大小和半衰期的变化模式，类似于对整个细胞的描述。在所研究的三个细胞系中，我们一致地解决了一个半小时在15到20小时之间的慢池。在平滑肌细胞中，只有慢池是明显的，而在Fu5AH中，也解决了一个非常大的快速池。与J774细胞相比，受体的载脂蛋白组成不影响这两种细胞系的载脂蛋白池。这些结果使我们提出了一个关于多个胆固醇动力学池对胆固醇从细胞膜解吸调节的影响的新模型。
Efflux of [14C]cholesterol from various cells was monitored in the presence of discoidal complexes of egg phosphatidylcholine and purified apolipoproteins, containing either apoAI, AII, or Cs. Particles containing apoAI were more efficient acceptors than those containing apoAII or Cs when the donor cells were J774 macrophages. No differences were observed when the same acceptor preparations were exposed to Fu5AH rat hepatoma or rabbit aortic smooth muscle cells. The differential efficiency of apolipoproteins in stimulating cholesterol removal from J774 cells was maintained in a plasma membrane-enriched fraction isolated from the same cells. Nonlinear regression analysis of kinetic data obtained from J774 cells exposed to apoAI complexes indicated that cholesterol efflux was best fitted to a curve describing the release from two kinetic compartments. Approximately 10% of cholesterol was transferred from a rapidly exchangeable pool with a t1/2 ranging between 1.5 and 3 h, and the remaining fraction was released from a slower pool with a t1/2 of about 20 h. Modulation of cholesterol efflux from J774 cells by either varying the concentration or the apolipoprotein composition of the acceptors influenced the size of the pools and the t1/2 of the slow pool. Kinetics of cholesterol efflux from membranes isolated from J774 cells also best fit a two-compartment model and modification of the apolipoprotein composition of the acceptor induced a pattern of changes in pool size and half-time similar to that described for whole cells. In the three cell lines studied, we consistently resolved a slow pool with a half-time ranging between 15 and 20 h. In smooth muscle cells only the slow pool was evident, whereas in Fu5AH a very large fast pool was also resolved. In contrast to J774 cells, apolipoprotein composition of the acceptor did not influence the pools in these two cell lines. These results led us to propose a new model regarding the influence of multiple kinetic pools of cholesterol on the regulation of cholesterol desorption from the cell membrane.