Oxygen-glucose deprivation regulates BACE1 expression through induction of autophagy in Neuro-2a/APP695 cells  

作　　者：Rong-fu Chen Ting Zhang Yin-yi Sun Ya-meng Sun Wen-qi Chen Nan Shi Fang Shen Yan Zhang Kang-yong Liu Xiao-jiang Sun 

机构地区：[1]Department of Neurology, Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University [2]Zhoupu Hospital

出　　处：《Neural Regeneration Research》2015年第9期1433-1440,共8页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.31171014,31371065;a grant from Shanghai Municipal Health Bureau,China,No.20134125;a grant from Shanghai Pudong District Health Bureau of China,No.PDZz2013-10

摘　　要：Our previous findings have demonstrated that autophagy regulation can alleviate the decline of learning and memory by eliminating deposition of extracellular beta-amyloid peptide （Aβ） in the brain after stroke, but the exact mechanism is unclear. It is presumed that the regulation of beta-site APP-deaving enzyme 1 （BACE1）, the rate-limiting enzyme in metabolism of Aβ, would be a key site. Neuro-2a/amyloid precursor protein 695 （APP695） cell models of cerebral isch- emia were established by oxygen-glucose deprivation to investigate the effects of Rapamycin （an autophagy inducer） or 3-methyladenine （an autophagy inhibitor） on the expression of BACE1. Either oxygen-glucose deprivation or Rapamycin down-regulated the expression of BACE1 while 3-methyladenine up-regulated BACE1 expression. These results confirm that oxygen-glucose deprivation down-regulates BACE1 expression in Neuro-2a/APP695 cells through the introduction of autophagy.Our previous findings have demonstrated that autophagy regulation can alleviate the decline of learning and memory by eliminating deposition of extracellular beta-amyloid peptide （Aβ） in the brain after stroke, but the exact mechanism is unclear. It is presumed that the regulation of beta-site APP-deaving enzyme 1 （BACE1）, the rate-limiting enzyme in metabolism of Aβ, would be a key site. Neuro-2a/amyloid precursor protein 695 （APP695） cell models of cerebral isch- emia were established by oxygen-glucose deprivation to investigate the effects of Rapamycin （an autophagy inducer） or 3-methyladenine （an autophagy inhibitor） on the expression of BACE1. Either oxygen-glucose deprivation or Rapamycin down-regulated the expression of BACE1 while 3-methyladenine up-regulated BACE1 expression. These results confirm that oxygen-glucose deprivation down-regulates BACE1 expression in Neuro-2a/APP695 cells through the introduction of autophagy.

关 键 词：nerve regeneration brain lnjury oxygen-glucose deprivation cerebral ischemia stroke AUTOPHAGY beta-site APP-cleaving enzyme 1 （BACE1） beta-amyloid peptide 3-methyladenine （3-MA） RAPAMYCIN neural regeneration 

分 类 号：R741[医药卫生—神经病学与精神病学]