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

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 overexpression 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.

• Authors: Jia-Hui Fan, Hui-Meng Song, Xia Zhang, Wei-Jie Yan, Song Han, Yan-Ling Yin
• Journal: Sheng li xue bao : [Acta physiologica Sinica] (Sheng Li Xue Bao) Vol. 73 Issue 1 Pg. 17-25 (Feb 25 2021) ISSN: 0371-0874 [Print] China
• PMID: 33665656 (Publication Type: Journal Article)

Chemical References

• SIRT3 protein, rat
• Sirt3 protein, mouse
• Sirtuin 3
• Sirtuins

Topics

• Animals
• Brain Ischemia
• Down-Regulation
• Infarction, Middle Cerebral Artery
• Mice
• Mitochondria
• Neurons (metabolism)
• Rats
• Reperfusion Injury
• Sirtuin 3 (genetics, metabolism)
• Sirtuins