MAPK信号通路介导CT-1促进大鼠心肌细胞存活  

MAPK mediates cardiac myocyte survival promoted by CT-1 in rats

作　　者：符史干[1] 董战玲[1] 周升[1] 翁启芳[1] 许闽广[1] 

机构地区：[1]海南医学院生理学教研室,海南海口571101

出　　处：《基础医学与临床》2007年第1期31-35,共5页Basic and Clinical Medicine

基　　金：国家自然科学基金(NaturalScienceFoundationofNation)(30260032)

摘　　要：目的探讨心脏营养素-1（CT-1）对培养乳鼠心肌细胞存活的促进作用以及丝裂原激活蛋白激酶（MAPK）信号传导途径在CT-1促进心肌细胞存活中的作用。方法差速贴壁纯化培养新生大鼠心肌细胞，MTT比色法测定各孔细胞存活率。结果无血清DMEM培养心肌细胞24h后，加入4个剂量组CT-1（10^-10～10^-7mol／L），呈明显剂量依赖性增加MTT计数；培养基中加入CT-1（10^-8mol／L），1、2、3和4dMTT计数呈明显的时间依赖性增加；预先用MAPK抑制剂PD098059（5×10^-5mol／L），再加入CT-1，心肌细胞存活率明显低于单纯CT-1组，而单纯用PD098059则无明显影响；预先用PKC激动剂PMA（10^-5mol／L），再加入CT-1，MTT计数明显增加；先用PD098059，再加入PMA和CT-1，MTT计数明显降低，而先用PKC抑制剂Calphostin C（Cal）再加CT-1，MTT计数也明显降低。结论CT-1增加心肌细胞存活率的效应是由MAPK信号分子介导实现的；该效应的胞内信号传导通路可能是先激活PKC信号分子，然后再激活MAPK信号分子。Objective Cardiac muscle ceils play a critical role in maintaining normal function of the heart. Cardiotrophin-1 （CT-1）, a potent cardiac survival factor, is capable of inhibiting apoptosis or promoting survival in cardiomyocytes. To elucidate the mechanism of CT-1 promoting cardiac myocyte survival in cultured neonatal rat cardiomyocytes. To explore the potential signaling pathway that might be responsible for this effect. Methods We examined the cardiac myocyte survival effect of CT-1 in cultured neonatal rat cardiomyocytes. The cardiomyocytes were stained [ 3- （4,5-dimethyl - thiaziazol-2-yl） -2-5-diphenyltetrazolium bromide, MTT ] and the counted. Results The survival rate of cardiac myocytes was increased by CT-1 in a dose-dependent manner （ 10^-10～10^-7 moL/L） and in a time-dependent manner（1～4 d, 10^-8 moL/L） in cultured neonatal rat cardiomyocytes. Pretreatment of PD098059 （5 x 10-SmoL/L） ,a MAPK blocker, decreased significantly survival rate of cardiac myocytes by promoted CT-1. The phorbol 12-myristate 13-acetate （PMA） （10^-5moL/L） ,a PKC activator, increased significantly this effect of CT-1, but inhibited significantly by MAPK blocker PD098059. Conclusion CT-1 is a potent factor of promoting cardiac myocyte survival, and increase significantly survival rate of cardiac myocytes in a dose-dependent and a time-dependent manner in cultured neonatal rat cardiomyocytes. The MAPK signaling pathway mediates CT-1 induced cardiac myocyte survival. PKC signaling molecule may be a upstream signaling transduction pathway which cascades of MAPK in CT-1 induced cardiac myocyte survival

关 键 词：心肌细胞培养 心脏营养素-1 丝裂原激活蛋白激酶 蛋白激酶C 

分 类 号：R363[医药卫生—病理学]