Ischemic accumulation of succinate induces Cdc42 succinylation and inhibits neural stem cell proliferation after cerebral ischemia/reperfusion
Lin-Yan Huang1
Ju-Yun Ma2
Jin-Xiu Song2
Jing-Jing Xu1
Rui Hong1
Hai-Di Fan2
Heng Cai2
Wan Wang1
Yan-Ling Wang1
Zhao-Li Hu3
Jian-Gang Shen4
Su-Hua Qi5
1.School of Medical Technology,Xuzhou Key Laboratory of Laboratory Diagnostics,Xuzhou Medical University,Xuzhou,Jiangsu Province,China2.College of Pharmacology,Xuzhou Medical University,Xuzhou,Jiangsu Province,China3.Research Center for Biochemistry and Molecular Biology and Jiangsu Key Laboratory of Brain Disease Bioinformation,Xuzhou Medical University,Xuzhou,Jiangsu Province,China4.School of Medical Technology,Xuzhou Key Laboratory of Laboratory Diagnostics,Xuzhou Medical University,Xuzhou,Jiangsu Province,China;School of Chinese Medicine,The University of Hong Kong,Hong Kong Special Administrative Region,China5.School of Medical Technology,Xuzhou Key Laboratory of Laboratory Diagnostics,Xuzhou Medical University,Xuzhou,Jiangsu Province,China;College of Pharmacology,Xuzhou Medical University,Xuzhou,Jiangsu Province,China;Research Center for Biochemistry and Molecular Biology and Jiangsu Key Laboratory of Brain Disease Bioinformation,Xuzhou Medical University,Xuzhou,Jiangsu Province,China
摘要：Ischemic accumulation of succinate causes cerebral damage by excess production of reactive oxygen species.However,it is unknown whether ischemic accumulation of succinate affects neural stem cell proliferation.In this study,we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery.We found that succinate levels increased in serum and brain tissue(cortex and hippocampus)after ischemia/reperfusion injury.Oxygen-glucose deprivation and reoxygenation stimulated primary neural stem cells to produce abundant succinate.Succinate can be converted into diethyl succinate in cells.Exogenous diethyl succinate inhibited the proliferation of mouse-derived C17.2 neural stem cells and increased the infarct volume in the rat model of cerebral ischemia/reperfusion injury.Exogenous diethyl succinate also increased the succinylation of the Rho family GTPase Cdc42 but repressed Cdc42 GTPase activity in C17.2 cells.Increasing Cdc42 succinylation by knockdown of the desuccinylase Sirt5 also inhibited Cdc42 GTPase activity in C17.2 cells.Our findings suggest that ischemic accumulation of succinate decreases Cdc42 GTPase activity by induction of Cdc42 succinylation,which inhibits the proliferation of neural stem cells and aggravates cerebral ischemia/reperfusion injury.
机标关键词：ischemiastemaftercellaccumulationcerebralinducesinhibits
论文发表日期：2023-05-28
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：6( 1040-1045 )
英文信息