AMYLOID β-PROTEIN STIMULATES TRAFFICKING OF CHOLESTEROL AND CAVEOLIN-1 FROM THE PLASMA MEMBRANE TO THE GOLGI COMPLEX IN MOUSE PRIMARY ASTROCYTES
AMYLOID β-PROTEIN STIMULATES TRAFFICKING OF CHOLESTEROL AND CAVEOLIN-1 FROM THE PLASMA MEMBRANE TO THE GOLGI COMPLEX IN MOUSE PRIMARY ASTROCYTES
复制标题
DOI：
10.1016/j.neuroscience.2009.04.049
复制
发表时间：
2009-08-18
期刊：
影响因子：
3.3
通讯作者：
Wood, W. G.
中科院分区：
文献类型：
--
作者：
Igbavboa, U.;Sun, G. Y.;Wood, W. G.
高尔基复合体在细胞胆固醇运输中发挥着关键作用。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复合体中的胆固醇分布和丰度。我们现在检验以下假设：Aβ 诱导的高尔基复合体胆固醇增加是由于胆固醇载体蛋白 Caveolin-1 从细胞质膜逆行到星形胶质细胞中的高尔基复合体所致。小鼠原代星形胶质细胞的结果表明，A beta(1-42) 诱导高尔基复合体中胆固醇和小窝蛋白丰度增加，同时质膜中胆固醇和小窝蛋白水平降低。用针对 Caveolin-1 mRNA 的 siRNA 转染的大鼠星形胶质细胞 (DITNC1) 抑制了 A beta(1-42) 诱导的胆固醇和 Caveolin 从质膜到高尔基复合体的重新分配。在未经 A beta(1-42) 处理的星形胶质细胞中，抑制 Caveolin-1 表达也显着降低了高尔基复合体中的胆固醇丰度，进一步证明了 Caveolin 在胆固醇从质膜逆行转运至高尔基复合体中的作用。 A beta(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。由 Elsevier Ltd 代表 IBRO 出版。
The Golgi complex plays a key role in cholesterol trafficking in cells. Our earlier study demonstrated amyloid beta-protein (A beta) alters cholesterol distribution and abundance in the Golgi complex of astrocytes. We now test the hypothesis that the A beta-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 A beta(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 A beta(1-42)-induced redistribution of both cholesterol and caveolin from the plasma membrane to the Golgi complex. In astrocytes not treated with A beta(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 A beta(1-42) could have consequences on membrane structure and cellular functions requiring optimal levels of cholesterol. Published by Elsevier Ltd on behalf of IBRO.