The role of autophagic and lysosomal pathways in ischemic brain injury******
Zhaohua Gu
Yinyi Sun
Kangyong Liu
Fen Wang
Ting Zhang
Qiang Li
Liwei Shen
Ling Zhou
Liang Dong
Nan Shi
Qian Zhang
Wei Zhang
Meizhen Zhao
Xiaojiang Sun
摘要： Autophagy is involved in neural cel death after cerebral ischemia. Our previous studies showed that rapamycin-induced autophagy decreased the rate of apoptosis, but the rate of apoptosis was creased after the autophagy inhibitor, 3-methyladenine, was used. In this study, a suture-occluded method was performed to generate a rat model of brain ischemia. Under a transmission electron microscope, autophagic bodies and autophagy lysosomes were markedly accumulated in neurons at 4 hours post brain ischemic injury, with their numbers gradual y reducing over time. Western blotting demonstrated that protein levels of light chain 3-II and cathepsin B were significantly in-creased within 4 hours of ischemic injury, but these levels were not persistently upregulated over time. Confocal microscopy showed that autophagy was mainly found in neurons with positive light chain 3 signal. Injection of rapamycin via tail vein promoted the occurrence of autophagy in rat brain tissue after cerebral ischemia and elevated light chain 3 and cathepsin B expression. However, in-jection of 3-methyladenine significantly diminished light chain 3-II and cathepsin B expression. Results verified that autophagic and lysosomal activity is increased in ischemic neurons. Abnormal components in cel s can be eliminated through upregulating cel autophagy or inhibiting autophagy after ischemic brain injury, resulting in a dynamic balance of substances in cel s. Moreover, drugs that interfere with autophagy may be potential therapies for the treatment of brain injury.
机标关键词：cerebral ischemiacathepsin Bischemic brain injuryelectron microscopebrain ischemiarat model
资助基金：grants from the National Natural Science Foundation of China, (No.31171014 and No.30970869)the Project of Science and Technology Commission of Shanghai City, (No.09DZ1950400)Board of Health of Shanghai, China, (No.2008086)the Youth Projects of National Natural Science Foundation of China, (No.31100783)Youth Key Project in Shanghai Col ege of Medicine of Fudan University, (No.09-L37)
论文发表日期：2013-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：9( 2117-2125 )
英文信息