MAPK mediates cardiac myocyte survival promoted by CT-1 in rats / 基础医学与临床

ABSTRACT

Objective Cardiac muscle cells 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?10-5mol/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-dependentand 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.