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Acute cerebral ischemia-induced down-regulation of Sirt3 protein expression contributes to neuronal injury via damaging mitochondrial function 

FAN Jia-Hui¹, SONG Hui-Meng¹, ZHANG Xia², YAN Wei-Jie¹, HAN Song¹, YIN Yan-Ling^1,*

¹ Department of Neurobiology, Capital Medical University, Beijing 100069, China；²Department of Physiology and Pathophysiology, Key Laboratory of Neurodegenerative Diseases of Ministry of Education, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China

Abstract

This study was aimed to determine the effect of acute cerebral ischemia on the protein expression level of silent mating type information regulator 2 homolog 3 (Sirt3) in the neurons and clarify the pathological role of Sirt3 in acute cerebral ischemia. The mice with middle cerebral artery occlusion (MCAO) and primary cultured rat hippocampal neurons with oxygen glucose deprivation (OGD) were used as acute cerebral ischemia models in vivo and in vitro, respectively. Sirt3 overexpression was induced in rat hippocampal neurons by lentivirus transfection. Western blot was utilized to measure the changes in Sirt3 protein expression level. CCK8 assay was used to detect cell viability. Immunofluorescent staining was used to detect mitochondrial function. Transmission electron microscope was used to detect mitochondrial autophagy. The results showed that, compared with the normoxia group, hippocampal neurons from OGD1 h/reoxygenation 2 h (R2 h) and OGD1 h/R12 h groups exhibited down-regulated Sirt3 protein expression levels. Compared with contralateral normal brain tissue, the ipsilateral penumbra region from MCAO1 h/reperfusion 24 h (R24 h) and MCAO1 h/R72 h groups exhibited down-regulated Sirt3 protein expression levels, while there was no significant difference between the Sirt3 protein levels on both sides of sham group. OGD1 h/R12 h treatment damaged mitochondrial function, activated mitochondrial autophagy and reduced cell viability in hippocampal neurons, whereas Sirt3 over-expression attenuated the above damage effects of OGD1 h/R12 h treatment. These results suggest that acute cerebral ischemia results in a decrease in Sirt3 protein level. Sirt3 over- expression can alleviate acute cerebral ischemia-induced neural injuries by improving the mitochondrial function. The current study sheds light on a novel  strategy against neural injuries caused by acute cerebral ischemia. 

Key words: SIRT3; mitochondria; acute cerebral ischemia; middle cerebral artery occlusion; oxygen glucose deprivation; hippocampal neurons

Received: 2020-04-02　　Accepted: 2020-09-18

Corresponding author: 尹艳玲　　E-mail: yyling@ccmu.edu.cn

DOI: 10.13294/j.aps.2021.0008

Citing This Article：

FAN Jia-Hui, SONG Hui-Meng, ZHANG Xia, YAN Wei-Jie, HAN Song, YIN Yan-Ling. Acute cerebral ischemia-induced down-regulation of Sirt3 protein expression contributes to neuronal injury via damaging mitochondrial function . Acta Physiol Sin 2021; 73 (1): 17-25 (in Chinese with English abstract).