Objectives Poly (ADP-ribose) polymerase (PARP) played an important role in the pathogenesis of heart ischaemia/reperfusion (I/R) injury. The mechanisms are still not thoroughly understood. Here we investigated the effect of PARP inhibition on heart I/R injury and elucidated the underlying mechanisms.
Methods Studies were performed with I/R rats' hearts. 3,4-dihydro-5-[4-(1-piperidinyl) butoxy]-1(2H)- isoquinolinone (DPQ) was used to inhibit the activate of PARP. The myocardial infarction size, cardiac function and cells apoptosis were detected. The activation of PARP, c-Jun NH2-terminal kinase (JNK) and Apoptosis-inducing factor (AIF) were evaluated during the I/R protocol.
Results Heart I/R caused a significant increase in PARP, JNK and AIF activity. Administration of DPQ decreased myocardial infarction size from 60.97±4.22% to 39.03±3.94% p<0.05) and cells apoptosis from 35±5.3% to 20±4.1% p<0.05) and simultaneously improved the cardiac function. Administration of DPQ reduced the activation of JNK and attenuated mitochondrial-nuclear translocation of AIF. Administration of SP600125 also attenuated mitochondrial-nuclear translocation of AIF.
Conclusions Our results suggested that the inhibition of PARP was able to reduce heart I/R injury. JNK may be downstream of PARP activation and be required for PARP mediated AIF translocation. Inhibition of the activity of PARP may reduce heart I/R injury via suppressing AIF translocation mediated by JNK.