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目的ERKs是钙依赖性激活蛋白,本研究旨在探讨钙依赖性蛋白激酶是否参与了脑缺血后ERK级联的调控。方法采用四动脉结扎诱导大鼠前脑缺血,用免疫印迹的方法观察几个钙依赖性蛋白激酶含量及活性的变化。结果致死性脑缺血以NMDA受体依赖的方式激活ERKs,并差异性上调Src和Ca2+/钙调蛋白依赖性蛋白激酶II(CaMKII)的活性。Src激酶和CaMKII的抑制剂PP2和KN62能显著的阻止缺血诱导的ERKs激活。然而,缺血诱导的Src过度激活也伴随着ERKs的活性抑制。结论致死性脑缺血刺激NMDA受体通过Src激酶和CaMKII介导ERKs活性上调,但是脑缺血诱导的Src过度激活可能也参与了ERKs信号通路的负性调控。
The purpose of ERKs is a calcium-dependent activator of protein, the purpose of this study is to explore whether calcium-dependent protein kinase involved in the regulation of ERK cascade after cerebral ischemia. Methods The forebrain ischemia was induced by four-artery ligation in rats. The changes of calcium-dependent protein kinase (PKC) content and activity were observed by immunoblotting. Results Fatal cerebral ischemia activated ERKs in an NMDA receptor-dependent manner and differentially up-regulated the activity of Src and Ca2 + / calmodulin-dependent protein kinase II (CaMKII). Src kinase and inhibitors of CaMKII PP2 and KN62 can significantly prevent ischemia-induced activation of ERKs. However, ischemia-induced Src overactivity is also accompanied by inhibition of ERKs activity. Conclusion Fatal ischemic neuronal activation induces up-regulation of ERKs via Src kinase and CaMKII, but over-activation of Src induced by cerebral ischemia may be involved in the negative regulation of ERKs signaling pathway.