c-Jun N-terminal kinase (JNK) signaling cascade regulates myocardial ischemia-reperfusion injury. We examined the ability of JNK inhibitor (JNKI) to improve the myocardial performance in hearts exposed to ischemia-reperfusion. JNKI was given during stabilization. After stabilization, the hearts were exposed to 30-min of global ischemia followed by 15 or 45-min of reperfusion. Five groups were studied: vehicle, TAT, D-JNKI 10, 50 and 250 mM. After 15-min of reperfusion, D-JNKI limited both JNK activity and c-jun phosphorylation induced by ischemia-reperfusion, but did not modified p38 and Extracellular signal Regulated Kinase (ERK) activation. At the end of ischemia, end-diastolic pressure (EDP) was significantly lower in treated groups with JNKI than vehicle and TAT groups. At the end of reperfusion, EDP was increased in both vehicle and TAT hearts. In contrast, it decreased significantly in hearts with JNKI compared to vehicle and TAT hearts in a dose-dependent manner. The recovery of rate x pressure product was improved with JNKI compared to vehicle and TAT groups. The improvement was more pronounced in D-JNKI 50 and 250 ìM groups. Also caspace-3 activity was significantly decreased in treated groups with JNKI compared to vehicle and TAT groups. In conclusion, JNKI protects the myocardium against ischemia-reperfusion in a dose-dependent manner and it selectively limits JNK activity.
|Titolo:||A peptide inhibitor of e-Jun N-terminal kinase protects the myocardium against ischemia-reperfusion injury|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Data di pubblicazione:||2006|
|Appare nelle tipologie:||01 - Articolo su periodico|