Inhibition of the activity of Rho-kinase reduces cardiomyocyte apoptosis in heart ischemia/reperfusion via suppressing 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.


METHODS
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.


CONCLUSIONS
The inhibition of Rho-kinase reduced cell apoptosis in I/R in vivo via suppression of JNK-mediated AIF translocation.
Zhang
Juan
J
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.
Li
Xiao-Xing
XX
Bian
Hong-Jun
HJ
Liu
Xiao-Bo
XB
Ji
Xiao-Ping
XP
Zhang
Yun
Y
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D048670:MAP Kinase Kinase 4 / Q000187:drug effects / Q000378:metabolism*; D009203:Myocardial Infarction / Q000201:enzymology* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology* / Q000473:pathology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
C494831:Aifm1 protein, rat; D000873:Anthracenes; D051033:Apoptosis Inducing Factor; D047428:Protein Kinase Inhibitors; C432165:pyrazolanthrone; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; D048670:MAP Kinase Kinase 4; C049347:fasudil