CaMKⅡ和SynGAP在大鼠脑缺血中的神经保护作用  

The neuroproctive role of CaMKⅡ and SynGAP in rats with brain ischemia

作　　者：宋波[1] 敖强[2] 公衍道[1] 

机构地区：[1]清华大学生命科学学院,北京市100084 [2]清华大学玉泉医院神经中心,北京市100049

出　　处：《实用医学杂志》2013年第20期3289-3291,共3页The Journal of Practical Medicine

基　　金：国家高技术研究发展计划863计划(编号:2012AA020905);国家自然科学基金(编号:81171143);清华-裕元医学科学研究基金

摘　　要：目的:研究脑缺血诱导的SynGAP丝氨酸磷酸化、CaMKⅡ与SynGAP的相互作用及内在机制。方法:利用大鼠四动脉结扎全脑缺血模型,通过免疫沉淀和免疫印迹的手段观察CaMKⅡ自身磷酸化、从胞浆转位到胞膜以及SynGAP的丝氨酸磷酸化,并利用脑室注射CaMKⅡ的特异性抑制剂观察上述指标的变化。结果:脑缺血导致胞膜部分总的CaMKⅡ和磷酸化的CaMKⅡ的水平均显著升高,CaMKⅡ与SynGAP的结合显著高于对照组,SynGAP的丝氨酸磷酸化水平也显著升高;CaMKⅡ的抑制剂KN62能抑制CaMKⅡ的自身磷酸化、SynGAP的丝氨酸磷酸化以及CaMKⅡ和SynGAP的相互结合,但对胞膜CaMKⅡ的水平没有影响。结论:脑缺血诱导的SynGAP丝氨酸磷酸化是由CaMKⅡ所催化的,SynGAP发生丝氨酸磷酸化后导致激活MAPK信号通路,在缺血过程中可能为一种细胞应激反应,对神经元起保护作用。Objective To investigate the effects of brain ischemia on the serine phosporylation of SynGAP and the interactions ofCaMKⅡ and SynGAP. Methods Brain ischemia was induced by four-vessel occlusion in Sprague-Dawley （SD） rats. By immunoprecipitation and immnoblot analysis, autophosphorylation and translocation of CaMKⅡ and serine phosporylation of SynGAP were examined. KN-62, a selective inhibitor of CaMKⅡ , was also used. Results During brain ischemia, the protein levels of CaMKⅡ and phosphorylated CaMKⅡ were all higher than the sham controls. The interaction between CaMKⅡ and SynGAP was markedly higher than the sham controls. The protein level of serine-phosphorylated SynGAP was significantly increased. KN-62 not only inhibited autophosphorylation of CaMKⅡ but also inhibited serine phosphorylation of SynGAP and the interaction between CaMKⅡ and SynGAP, but had no effect on the protein level of CaMKⅡ. Conclusions CaMKⅡ is responsible for the serine phosphorylation of SynGAP in brain ischemia. The phosphorylation and inhibition of SynGAP may result in activation of MAP kinase pathway, which may be a type of cellular stress response to exert a protective action on brain ischemia.

关 键 词：脑缺血 CA2+ CaM依赖的蛋白激酶Ⅱ 突触Ras—GTP酶激活蛋白 丝氨酸磷酸化 神经保护 

分 类 号：R741[医药卫生—神经病学与精神病学]