过表达SHP1能够阻断BACE1通过自噬降解途径降解以及促进ROS的上升
Overexpression of SHP1 blocks BACE1 degradation through autophagy and induces ROS in the Alzheimer\'s disease
目的：探讨在阿尔兹海默症（AD）中，蛋白酪氨酸磷酸酶（SHP1）的作用以及分子作用。方法：（1）通过检测AD模型小鼠（APP/PS1小鼠）以及APP稳转细胞系中的SHP1，β-分泌酶（BACE1）以及相关自噬指标蛋白（LC3）。（2）通过免疫共沉淀的方法检测SHP1与自噬指标蛋白LC3，以及BACE1蛋白之间的关系。（3）在HEK-APP细胞系中过表达SHP1，用免疫荧光和Westernblot的方法检测自噬的变化。（4）在HEK-APP细胞系中过表达SHP1,检测BACE1蛋白的水平。（5）用Mito-sox试剂盒检过表达SHP1后活性氧（ROS）的水平。结果：（1）APP/PS1小鼠中BACE1和SHP1蛋白水平上升。（2）SHP1能够与BACE1以及LC3相结合。（3）过表达SHP1会导致自噬流障碍。（4）过表达SHP1会导致BACE1的蛋白积累。（5）过表达SHP1会诱导细胞内ROS上升。结论：在AD中，SHP1蛋白水平增加，以及诱导自噬流障碍，从而阻断BACE1蛋白通过自噬降解，并且会诱导ROS增加。
Recent studies have indicated SHP1(Src homology region 2 domain-containing phosphatase-1) play an important role in autophagosome biogenesis. Further, defects in autophagy are likely to contribute to the neurodegenerative processes in numerous diseases, including Alzheimer\'s disease (AD). However, the role of SHP1 in the AD is rarely reported. Here, our study indicates that compared with normal mice and cells, the SHP1 is increased in APP/PS1 transgenic mice and HEK-APP cells. We show that SHP1, BACE1, andLC3 can form a complex compound. Overexpression of SHP1 increases the level of reactive oxygen species (ROS) and causes autophagy dysfunction. We further demonstrate that overexpression of SHP1 protein inhibits BACE1 protein degradation through autophagy. Thus, these results indicate SHP1 may be a potential risk factor in Alzheimer\'s disease.
方礼跑、韩晶晶、马全红、刘洋
基础医学神经病学、精神病学分子生物学
神经生物学BACE1SHP1自噬
NeurobiologyBACE1SHP1Autophagy
方礼跑,韩晶晶,马全红,刘洋.过表达SHP1能够阻断BACE1通过自噬降解途径降解以及促进ROS的上升[EB/OL].(2018-08-03)[2025-04-26].http://www.paper.edu.cn/releasepaper/content/201808-14.点此复制
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