Patel S C, Asotra K, Patel Y C, Patel R C, Suresh S
Department of Neurology, University of Connecticut Health Center, Farmington 06030.
Neuroreport. 1994 Oct 27;5(16):2121-4. doi: 10.1097/00001756-199410270-00033.
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.
25-羟基胆固醇（25-OHC）是一种能有效调节细胞胆固醇代谢的氧化甾醇，用胆固醇探针制霉菌素进行荧光显微镜观察时，可发现其能诱导正常小鼠星形胶质细胞形成新型纤维状结构。通过对溶酶体相关膜糖蛋白（LAMP）的免疫反应性，这些纤维被鉴定为溶酶体。相比之下，源自尼曼-匹克病C型（NPC）突变小鼠的星形胶质细胞对这种氧化甾醇诱导的溶酶体重组具有抗性。通过对NPC星形胶质细胞溶酶体进行亮阳性制霉菌素染色可观察到，其细胞内胆固醇储存异常。这些结果表明，NPC星形胶质细胞中的溶酶体胆固醇储存与氧化甾醇介导的溶酶体纤维状重组受阻有关。
