2. Academic Validation
  3. Downregulation of mitochondrial pyruvate carrier 2 aggravates neuronal injury in the cortex following cerebral ischemia in rat

Downregulation of mitochondrial pyruvate carrier 2 aggravates neuronal injury in the cortex following cerebral ischemia in rat

  • Brain Res Bull. 2022 Jul;185:193-202. doi: 10.1016/j.brainresbull.2022.05.007.
Yue Wang 1,  Yue Liu 2,  Yuan Yuan 3,  Ying Zhang 4,  Yanlin Luo 5,  Song Han 6,  Yi Yan 7,  Zhaohui Wang 8,  Xiao Liu 9,  Li Zhao 10
Affiliations

Affiliations

  • 1 The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, PR China. Electronic address: wangyue@ccmu.edu.cn.
  • 2 Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China. Electronic address: lingyueyue@mail.ccmu.edu.cn.
  • 3 Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China. Electronic address: farfargirl@aliyun.com.
  • 4 Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China. Electronic address: yingzhang@ccmu.edu.cn.
  • 5 Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China. Electronic address: luoyl@ccmu.edu.cn.
  • 6 Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China. Electronic address: songhan@ccmu.edu.cn.
  • 7 Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China. Electronic address: yysfn@126.com.
  • 8 Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China. Electronic address: 15617870117@163.com.
  • 9 Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China. Electronic address: 17860752269@163.com.
  • 10 Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China. Electronic address: zhaoli@ccmu.edu.cn.
PMID: 35580702 DOI: 10.1016/j.brainresbull.2022.05.007
Abstract

Cerebral ischemia is one of the most common disabling and lethal diseases worldwide, but its underlying mechanisms remain unclear. Mitochondrial pyruvate carrier 2 (MPC2), a subunit of MPC complex, plays pivotal roles in coordinating glycolytic and mitochondrial activities. In the present study, the expression of MPC2 was significantly reduced in the ischemic cerebral cortex of rats at 24 h after bilateral internal carotid artery occlusion (BICAO), and in the cortical neurons after 1 h oxygen-glucose deprivation (OGD)/24 h reoxygenation treatment. After MPC2 gene knockdown, the number and expression of neurons were remarkably decreased in the ischemic cerebral cortex of BICAO rats and OGD-treated neurons. UK5099 significantly reduced the number, expression and viability of OGD-treated neurons, and resulted in a significant decrease in length of neurite. Using RNA-sequencing (RNA-seq) technique, we further identified MPC2-related differential genes in the ischemic cerebral cortex of BICAO rats. In conclusion, our results suggested that the decrease in MPC2 expression aggravated ischemic injury, and MPC2-related genes might be a novel therapeutic target for cerebral ischemia.

Keywords

Bilateral internal carotid artery occlusion (BICAO); Mitochondrial pyruvate carrier 2 (MPC2); Neuron; RNA-sequencing (RNA-seq) technique.

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