Lin Yu-Chun, Ma Chang, Hsu Wei-Ching, Lo Hsiao-Fan, Yang Vivian C
Department of Life Science, Tunghai University, Taichung, Taiwan, ROC.
Cardiovasc Res. 2007 Aug 1;75(3):575-83. doi: 10.1016/j.cardiores.2007.04.012. Epub 2007 Apr 21.
Caveolin-1 and ATP-binding cassette transporter A1 (ABCA1) are proteins that are involved in cellular cholesterol efflux. In this study, we analyzed the relationships between caveolin-1 and ABCA1 on high-density lipoprotein (HDL)-mediated cholesterol efflux in rat aortic endothelial cells.
Overexpression of caveolin-1 by transfection with caveolin-1 cDNA in aortic endothelial cells up-regulated ABCA1 expression and enhanced cholesterol efflux. Suppression of caveolin-1 by siRNA decreased ABCA1 expression and reduced cholesterol efflux. The number of caveolae increased after transfection with caveolin-1 into cells. Immunoprecipitation assays revealed a molecular interaction between caveolin-1 and ABCA1 in the plasma membrane and in the cytoplasm after HDL incubation. Immunoelectron microscopy demonstrated that caveolin-1 colocalized with ABCA1 in the caveolae and in the cytoplasmic vesicles; it was also found that caveolin-1 and ABCA1 colocalized with cellular cholesterol by immunofluorescence microscopy. Blocking of intracellular lipid transport by inhibitors disrupted the interaction between caveolin-1 and ABCA1 and reduced cholesterol to methyl-beta-cyclodextrin and HDL.
The molecular interaction between caveolin-1 and ABCA1 is associated with the HDL-mediated cholesterol efflux pathway in aortic endothelial cells.
小窝蛋白-1和ATP结合盒转运蛋白A1（ABCA1）是参与细胞胆固醇外流的蛋白质。在本研究中，我们分析了大鼠主动脉内皮细胞中，小窝蛋白-1与ABCA1在高密度脂蛋白（HDL）介导的胆固醇外流中的关系。
通过在主动脉内皮细胞中转染小窝蛋白-1 cDNA来过表达小窝蛋白-1，可上调ABCA1表达并增强胆固醇外流。用小干扰RNA（siRNA）抑制小窝蛋白-1可降低ABCA1表达并减少胆固醇外流。将小窝蛋白-1转染到细胞中后，小窝数量增加。免疫沉淀试验显示，在HDL孵育后，质膜和细胞质中存在小窝蛋白-1与ABCA1的分子相互作用。免疫电子显微镜显示，小窝蛋白-1与ABCA1在小窝和细胞质囊泡中共定位；通过免疫荧光显微镜还发现，小窝蛋白-1和ABCA1与细胞胆固醇共定位。用抑制剂阻断细胞内脂质转运可破坏小窝蛋白-1与ABCA1之间的相互作用，并减少胆固醇向甲基-β-环糊精和HDL的转运。
小窝蛋白-1与ABCA1之间的分子相互作用与主动脉内皮细胞中HDL介导的胆固醇外流途径相关。
