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

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

  • Clin Chim Acta. 2009 Mar;401(1-2):76-80. doi: 10.1016/j.cca.2008.11.016.
Juan Zhang 1,  Xiao-Xing Li,  Hong-Jun Bian,  Xiao-Bo Liu,  Xiao-Ping Ji,  Yun Zhang
Affiliations

Affiliation

  • 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.
PMID: 19061880 DOI: 10.1016/j.cca.2008.11.016
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.

Figures
Products