Intracellular cholesterol mobilization involved in the ABCA1/apolipoprotein-mediated assembly of high density lipoprotein in fibroblasts Published, JLR Papers in Press, August 1, 2004. DOI 10.1194/jlr.M400264-JLR200
Intracellular cholesterol mobilization involved in the ABCA1/apolipoprotein-mediated assembly of high density lipoprotein in fibroblasts Published, JLR Papers in Press, August 1, 2004. DOI 10.1194/jlr.M400264-JLR200
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DOI：
10.1194/jlr.m400264-jlr200
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发表时间：
2004-10
影响因子：
6.5
通讯作者：
Y. Yamauchi;C. Chang;M. Hayashi;S. Abe-Dohmae;P. Reid;Ta-Yuan Chang;S. Yokoyama
中科院分区：
文献类型：
--
作者：
Y. Yamauchi;C. Chang;M. Hayashi;S. Abe-Dohmae;P. Reid;Ta-Yuan Chang;S. Yokoyama
载脂蛋白A-I(apoA-I)/ABCA1对细胞胆固醇和磷脂的释放有不同的调节作用。我们研究了与这一途径相关的胆固醇动员的各种因素。ApoA-I诱导了细胞内胆固醇隔间的快速减少，该隔室与ACAT可获得的池平衡，从而产生富含胆固醇的高密度脂蛋白。ACAT的药理和遗传失活通过上调ABCA1和通过增加生成的高密度脂蛋白中的胆固醇来增强apoA-I介导的胆固醇释放。蛋白激酶C(PKC)的药理激活也减少了ACAT可获得的胆固醇池，不仅在由apoA-I产生高胆固醇高密度脂蛋白的细胞(即人成纤维细胞WI-38细胞)中，而且在产生低胆固醇高密度脂蛋白的细胞(小鼠成纤维细胞L929细胞)中也是如此。在L929细胞中，PKC的激活导致apoA-I介导的胆固醇释放增加，而磷脂释放和ABCA1表达没有检测到变化。这些结果表明，apoA-I动员细胞内胆固醇从ACAT控制的隔室释放ABCA1介导的胆固醇。胆固醇动员过程可能与apoA-I激活PKC有关。
Differential regulation has been suggested for cellular cholesterol and phospholipid release mediated by apolipoprotein A-I (apoA-I)/ABCA1. We investigated various factors involved in cholesterol mobilization related to this pathway. ApoA-I induced a rapid decrease of the cellular cholesterol compartment that is in equilibrium with the ACAT-accessible pool in cells that generate cholesterol-rich HDL. Pharmacological and genetic inactivation of ACAT enhanced the apoA-I-mediated cholesterol release through upregulation of ABCA1 and through cholesterol enrichment in the HDL generated. Pharmacological activation of protein kinase C (PKC) also decreased the ACAT-accessible cholesterol pool, not only in the cells that produce cholesterol-rich HDL by apoA-I (i.e., human fibroblast WI-38 cells) but also in the cells that generate cholesterol-poor HDL (mouse fibroblast L929 cells). In L929 cells, the PKC activation caused an increase in apoA-I-mediated cholesterol release without detectable change in phospholipid release and in ABCA1 expression. These results indicate that apoA-I mobilizes intracellular cholesterol for the ABCA1-mediated release from the compartment that is under the control of ACAT. The cholesterol mobilization process is presumably related to PKC activation by apoA-I.