Knockdown of RGMA improves ischemic stroke via Reprogramming of Neuronal Metabolism

作者全名：Wang, Zijie; Zhang, Shaoru; Cheng, Ruiqi; Jiang, Anan; Qin, Xinyue

作者地址：[Wang, Zijie; Zhang, Shaoru; Cheng, Ruiqi; Jiang, Anan; Qin, Xinyue] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing 400016, Peoples R China

通信作者：Qin, XY (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing 400016, Peoples R China.

来源：FREE RADICAL BIOLOGY AND MEDICINE

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001226208300001

JCR分区：Q1

影响因子：7.1

年份：2024

卷号：218

期号：　

开始页：41

结束页：56

文献类型：Article

关键词：RGMA; Ischemic stroke; Metabolism; USP10; PGK1

摘要：Neuronal energy metabolism dysregulation is involved in various pathologies of Ischemia-reperfusion (I/R), yet the role of RGMA in neuronal metabolic reprogramming has not been reported. In this study, we found that RGMA expression significantly increased after I/R, and compared to control mice, mice with MCAO/R showed an increase in glycolytic metabolic products and the expression of glycolytic pathway proteins. Furthermore, RGMA levels are closely related to neuronal energy metabolism. We discovered that knockdown of RGMA can shift neuronal energy metabolism towards oxidative phosphorylation and the pentose phosphate pathway, thereby protecting mice from ischemic reperfusion injury. Mechanistically, knockdown of RGMA can downregulate PGK1 expression, reducing the increase in glycolytic flux following ischemia reperfusion. Moreover, we found that knockdown of RGMA can reduce the interaction between USP10 and PGK1, thus affecting the ubiquitination degradation of PGK1. In summary, our data suggest that RGMA may regulate neuronal energy metabolism by inhibiting the USP10-mediated deubiquitination of PGK1, thus protecting it from I/R injury. This study provides new ideas for clarifying the intrinsic mechanism of neuronal damage after I/R.

基金机构：National Natural Science Foundation of China [82071338, 82101375]; First Affiliated Hospital of Chongqing Medical University's "Discipline Summit Plan" [cyyy-xkdfjh-jcyj-202309]

基金资助正文：This study was supported by the National Natural Science Foundation of China (NO.82071338) and (NO.82101375) . This study was supported by the First Affiliated Hospital of Chongqing Medical Uni- versity's "Discipline Summit Plan" (cyyy-xkdfjh-jcyj-202309) .