Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention  

作　　者：Ju Zheng Yixin Li Ting Zhang Yanlin Fu Peiyan Long Xiao Gao Zhengwei Wang Zhizhong Guan Xiaolan Qi Wei Hong Yan Xiao 

机构地区：[1]Key Laboratory of Endemic and Ethnic Diseases,Ministry of Education&Key Laboratory of Medical Molecular Biology of Guizhou Province,Guizhou Medical University,Guiyang,Guizhou Province,China [2]Guizhou Center for Disease Control and Prevention,Guiyang,Guizhou Province,China [3]Department of Histology and Embryology,Guizhou Medical University,Guiyang,Guizhou Province,China [4]Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry,Guiyang,Guizhou Province,China

出　　处：《Neural Regeneration Research》2025年第5期1455-1466,共12页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.82260245(to YX),81660207(to YX),81960253(to YL),82160268(to YL),U1812403(to ZG);Science and Technology Projects of Guizhou Province,Nos.[2019]1440(to YX),[2020]1Z067(to WH);Cultivation Foundation of Guizhou Medical University,No.[20NSP069](to YX);Excellent Young Talents Plan of Guizhou Medical University,No.(2022)101(to WH)。

摘　　要：Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

关 键 词：APOPTOSIS ATF4 AUTOPHAGY C/EBP homologous protein cerebral ischemia/reperfusion injury EIF2Α endoplasmic reticulum stress PERK 

分 类 号：R743.3[医药卫生—神经病学与精神病学]