Inhibition of the activity of Rho-kinase reduces cardiomyocyte apoptosis in heart ischemia/reperfusion via suppressing JNK-mediated AIF translocation

BackgroundRecent studies have demonstrated that Rho-kinase has been proposed to play an important role in the pathogenesis of heart ischemia/reperfusion (I/R) injury. However, the mechanism of Rho-kinase mediated cardiomyocyte apoptosis in I/R is still not thoroughly understood.MethodStudies were performed with female Wistar rats.ResultsIschemia followed by reperfusion caused a significant increase in Rho-kinase, c-Jun NH2-terminal kinase (JNK) and apoptosis-inducing factor (AIF) activity. Administration of fasudil, an inhibitor of Rho-kinase, decreased myocardial infarction size from 59.89 ± 3.83% to 38.62 ± 2.66% (P < 0.05) and cell apoptosis from 32.78 ± 5.1% to 17.05 ± 4.2% (P < 0.05). Western blot analysis showed that administration of fasudil reduced the activation of JNK and attenuated mitochondrial-nuclear translocation of AIF. Additionally, administration of SP600125, an inhibitor of JNK, attenuated mitochondrial-nuclear translocation of AIF.ConclusionThe inhibition of Rho-kinase reduced cell apoptosis in I/R in vivo via suppression of JNK-mediated AIF translocation.