南方医科大学学报2024，Vol.44Issue(3)：563-570,8.DOI:10.12122/j.issn.1673-4254.2024.03.18
CaMKⅡγ和CaMKⅡδ通过PI3K/Akt/Erk信号通路减轻小鼠神经元缺血再灌注损伤
PI3K/Akt/Erk signaling pathway mediates neuroprotection of CaMKⅡγ and CaMKⅡδ against ischemic reperfusion injury in mice
摘要
Abstract
Objective To observe neuroprotective effects of Ca2+/calmodulin-dependent kinase Ⅱ(CaMKⅡ)γ and CaMkⅡ δ against acute neuronal ischemic reperfusion injury in mice and explore the underlying mechanism.Methods Primary cultures of brain neurons isolated from fetal mice(gestational age of 18 days)were transfected with two specific siRNAs(si-CAMK2G and si-CAMK2D)or a control sequence(si-NT).After the transfection,the cells were exposed to oxygen-glucose deprivation/reperfusion(OGD/R)conditions for 1 h followed by routine culture.The expressions of phosphatidylinositol-3-kinase/extracellular signal-regulated kinase(PI3K/Akt/Erk)signaling pathway components in the neurons were detected using immunoblotting.The expressions of the PI3K/Akt/Erk signaling pathway proteins were also detected in the brain tissues of mice receiving middle cerebral artery occlusion(MCAO)or sham operation.Results The neuronal cells transfected with si-CAMK2G showed significantly lower survival rates than those with si-NT transfection at 12,24,48,and 72 h after OGD/R(P<0.01),and si-CAMK2G transfection inhibited OGD/R-induced upregulation of CaMKⅡγ expression.Compared to si-NT,transfection with si-CAMK2G and si-CAMK2D both significantly inhibited the expressions of PI3K/Akt/Erk signaling pathway components(P<0.01).In the mouse models of MCAO,the expressions of CaMKⅡδ and CaMKⅡγ were significantly increased in the brain,where activation of the PI3K/Akt/Erk signaling pathway was detected.The expression levels of CaMKⅡδ,CaMKⅡγ,Erk,phosphorylated Erk,Akt,and phosphorylated Akt were all significantly higher in MCAO mice than in the sham-operated mice at 24,48,72,and 96 h after reperfusion(P<0.05).Conclusion The neuroprotective effects of CaMKⅡδ and CaMKⅡγ against acute neuronal ischemic reperfusion injury are mediated probably by the PI3K/Akt/Erk pathway.关键词
脑缺血再灌注损伤/钙/钙调蛋白依赖性激酶Ⅱ/神经保护/磷脂酰肌醇-3-激酶/细胞外信号调节激酶/信号通路Key words
cerebral ischemia/reperfusion injury/Ca2+/calmodulin-dependent kinaseⅡ/neuroprotection/phosphatidylinositol-3-kinase/extracellular signal-regulated kinase/signaling pathway引用本文复制引用
刘昊铭,林子诗,叶靖..CaMKⅡγ和CaMKⅡδ通过PI3K/Akt/Erk信号通路减轻小鼠神经元缺血再灌注损伤[J].南方医科大学学报,2024,44(3):563-570,8.基金项目
广东省自然科学基金(2019A1515011190) （2019A1515011190）
广东省高等教育教学改革项目 （）
