25‐Hydroxycholesterol induces reorganization of lysosomes in normal but not Niemann‐Pick disease type C astrocytes
25‐Hydroxycholesterol induces reorganization of lysosomes in normal but not Niemann‐Pick disease type C astrocytes
复制标题
25-羟基胆固醇诱导正常但非尼曼-匹克病 C 型星形胶质细胞的溶酶体重组
作者：
Shutish C. Patel;K. Asotra;Y. Patel;Ramesh C. Patel;S. Suresh
25-羟基胆固醇（25-OHC）是一种有效调节细胞胆固醇代谢的氧固醇，通过胆固醇探针菲律平的荧光显微镜观察，在正常小鼠星形胶质细胞中诱导形成新的纤维状结构。这些原纤维通过它们对溶酶体相关膜糖蛋白（LAMP）的免疫反应性被鉴定为溶酶体。相反，来自C型尼曼-皮克病（NPC）突变小鼠的星形胶质细胞对氧固醇诱导的溶酶体重组具有抗性。星形胶质细胞内的胆固醇储存异常，其溶酶体呈亮阳性的菲律宾染色。这些结果表明，在NPC星形胶质细胞中的溶酶体胆固醇储存与氧化固醇介导的溶酶体纤维重组的阻断有关。
25-HYDROXYCHOLESTEROL (25-OHC), an oxysterol that potently regulates cellular cholesterol metabolism, induced formation of novel fibrillar structures in normal mouse astrocytes as observed by fluorescence microscopy with the cholesterol probe, filipin. These fibrils were identified as lysosomes by their immunoreactivity for the lysosome associated membrane glycoprotein (LAMP). In contrast, astrocytes derived from the Niemann-Pick disease type C (NPC) mutant mouse were resistant to this oxysterol-induced lysosomal reorganization. NPC astrocytes have abnormal intracellular cholesterol storage as observed by brightly positive filipin staining of their lysosomes. These results show that lysosomal cholesterol storage in NPC astrocytes is associated with a block in oxysterol-mediated fibrillar reorganization of lysosomes.