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Experimental Models to Study the Neuroprotection of Acidic Postconditioning Against Cerebral Ischemia
Published on: July 31, 2017
N6-methyladenosine demethylase ALKBH5 mediates remote ischemic postconditioning in cerebral ischemia-reperfusion
Aimei Wang1, Weiqi Wu1, Yin Mei1
1Department of Neurology, the Second Affiliated Hospital of Kunming Medical University, No.374 Dianmian Avenue, Kunming, Yunnan 650101, China.
None:
This study aimed to investigate the role of the m6A demethylase ALKBH5 in RIPostC against CI/R injury and its underlying regulatory mechanism. A rat model of CI/R was established using the MCAO method. Subsequently, RIPostC was performed to evaluate its therapeutic potential against CI/R injury. The effects of overexpressing ALKBH5 and KLF4 on CI/R injury were also examined in the rat model. A cellular model of CI/R was established by inducing OGD/R in PC12 cells. The effects of ALKBH5 and KLF4 on cellular function in the CI/R model were investigated, and the specific regulatory role of ALKBH5 in the m6A modification of KLF4 was elucidated. The mRNA expression of ALKBH5 and KLF4 in acute ischemic stroke patients and healthy individuals was measured by RT-qPCR. The results demonstrated that ALKBH5 and KLF4 expression was decreased in acute ischemic stroke patients, as well as in CI/R rats and OGD/R-induced cells. RIPostC treatment alleviated MCAO-induced neurological deficits, reduced cerebral infarct volume, apoptosis, and inflammatory cytokine levels. Furthermore, RIPostC upregulated the expression of ALKBH5 and KLF4 in CI/R rats. Overexpression of ALKBH5 and KLF4 further enhanced the therapeutic efficacy of RIPostC in CI/R rats. Overexpression of ALKBH5 and KLF4 alleviated OGD/R-induced cellular injury. Mechanistically, overexpression of ALKBH5 upregulated KLF4 expression by promoting m6A demethylation of KLF4 mRNA. In conclusion, overexpression of ALKBH5 upregulates KLF4 by promoting m6A demethylation, thereby attenuating CI/R injury.
