Juan Zhang1, Xiao-Xing Li, Hong-Jun Bian, Xiao-Bo Liu, Xiao-Ping Ji, Yun Zhang. 1. The Key Laboratory of Cardiovascular Remodeling and Function Research of Chinese Ministry of Education and Public Health, Shandong University Qilu Hospital, 250012 Jinan, Shandong Province, China.
Abstract
BACKGROUND: Recent 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. METHOD: Studies were performed with female Wistar rats. RESULTS: Ischemia 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. CONCLUSION: The inhibition of Rho-kinase reduced cell apoptosis in I/R in vivo via suppression of JNK-mediated AIF translocation.
BACKGROUND: Recent 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. METHOD: Studies were performed with female Wistar rats. RESULTS:Ischemia 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. CONCLUSION: The inhibition of Rho-kinase reduced cell apoptosis in I/R in vivo via suppression of JNK-mediated AIF translocation.
Authors: Sree Rayavarapu; Jack H Van der Meulen; Heather Gordish-Dressman; Eric P Hoffman; Kanneboyina Nagaraju; Susan M Knoblach Journal: PLoS One Date: 2010-09-24 Impact factor: 3.240