Ali-Khan Z, Chan S L, Jung S S, Chronopoloulos S
Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.
Neuroreport. 1996 Dec 20;8(1):385-9. doi: 10.1097/00001756-199612200-00075.
Chloroquine (CHQ)-sensitive cellular compartments, identified as endosomes-lysosomes (ELs), have been implicated in the proteolysis of amyloid beta precursor protein (A beta PP) in Alzheimer's disease. Here we show using immunocytochemistry and immunogold electron microscopy that not only A beta PP but also ubiquitin (Ub) co-localize to ELs in CHQ-treated human neuroblastoma (SK-N-SH) and glioblastoma (U-373). Immunoblotting analysis of cell lysates indicated a significant degree of CHQ-mediated interference in A beta PP metabolism in a time- and concentration-dependent manner. The implication is that abnormal intracellular accumulation of A beta PP and its C-terminal fragments beyond a certain threshold may trigger the Ub response. We hypothesize that Ub may play a role in A beta PP processing and/or trafficking to ELs, particularly in stress-related conditions.
氯喹（CHQ）敏感的细胞区室，被鉴定为内体-溶酶体（ELs），已被认为与阿尔茨海默病中淀粉样β前体蛋白（AβPP）的蛋白水解有关。在这里，我们使用免疫细胞化学和免疫金电子显微镜显示，不仅AβPP，而且泛素（Ub）在CHQ处理的人神经母细胞瘤（SK-N-SH）和胶质母细胞瘤（U-373）中都与ELs共定位。细胞裂解物的免疫印迹分析表明，CHQ以时间和浓度依赖性方式对AβPP代谢产生显著干扰。这意味着AβPP及其C末端片段在细胞内异常积累超过一定阈值可能会触发泛素反应。我们假设泛素可能在AβPP的加工和/或向ELs的运输中起作用，特别是在与应激相关的情况下。
