Igbavboa U, Sun G Y, Weisman G A, He Yan, Wood W G
Department of Pharmacology, University of Minnesota School of Medicine and Geriatric Research, Education and Clinical Center, VA Medical Center, 6-120 Jackson Hall, 321 Church Street Southeast, Minneapolis, MN 55455, USA.
Neuroscience. 2009 Aug 18;162(2):328-38. doi: 10.1016/j.neuroscience.2009.04.049. Epub 2009 May 3.
The Golgi complex plays a key role in cholesterol trafficking in cells. Our earlier study demonstrated amyloid beta-protein (Abeta) alters cholesterol distribution and abundance in the Golgi complex of astrocytes. We now test the hypothesis that the Abeta-induced increase in Golgi complex cholesterol is due to retrograde movement of the cholesterol carrier protein caveolin-1 from the cell plasma membrane to the Golgi complex in astrocytes. Results with mouse primary astrocytes indicated that Abeta(1-42)-induced increase in cholesterol and caveolin abundance in the Golgi complex was accompanied by a reduction in cholesterol and caveolin levels in the plasma membrane. Transfected rat astrocytes (DITNC1) with siRNA directed at caveolin-1 mRNA inhibited the Abeta(1-42)-induced redistribution of both cholesterol and caveolin from the plasma membrane to the Golgi complex. In astrocytes not treated with Abeta(1-42), suppression of caveolin-1 expression also significantly reduced cholesterol abundance in the Golgi complex, further demonstrating the role for caveolin in retrograde transport of cholesterol from the plasma membrane to the Golgi complex. Perturbation of this process by Abeta(1-42) could have consequences on membrane structure and cellular functions requiring optimal levels of cholesterol.
高尔基体复合物在细胞内胆固醇运输中起关键作用。我们早期的研究表明，淀粉样β蛋白（Aβ）会改变星形胶质细胞高尔基体复合物中胆固醇的分布和丰度。我们现在检验这样一个假设，即Aβ诱导的高尔基体复合物中胆固醇增加是由于胆固醇载体蛋白小窝蛋白-1在星形胶质细胞中从细胞质膜向高尔基体复合物的逆向转运所致。对小鼠原代星形胶质细胞的研究结果表明，Aβ（1-42）诱导的高尔基体复合物中胆固醇和小窝蛋白丰度增加伴随着质膜中胆固醇和小窝蛋白水平的降低。用针对小窝蛋白-1 mRNA的siRNA转染大鼠星形胶质细胞（DITNC1）可抑制Aβ（1-42）诱导的胆固醇和小窝蛋白从质膜向高尔基体复合物的重新分布。在未用Aβ（1-42）处理的星形胶质细胞中，小窝蛋白-1表达的抑制也显著降低了高尔基体复合物中胆固醇的丰度，进一步证明了小窝蛋白在胆固醇从质膜向高尔基体复合物逆向转运中的作用。Aβ（1-42）对这一过程的干扰可能会对需要最佳胆固醇水平的膜结构和细胞功能产生影响。
