Inhibition of the activity of poly (ADP-ribose) polymerase reduces heart ischaemia/reperfusion injury via suppressing JNK-mediated AIF translocation.
Poly (ADP-ribose) polymerase (PARP) has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion (I/R) injury. However, the mechanisms of PARP-mediated heart I/R injury in vivo are still not thoroughly understood. Therefore, in this study, we investigate the effect of PARP inhibition on heart I/R injury and try to elucidate the underlying mechanisms. Studies were performed with I/R rats' hearts in vivo. Ischaemia followed by reperfusion caused a significant increase in Poly (ADP-ribose) (PAR), c-Jun NH2-terminal kinase (JNK) and apoptosis-inducing factor (AIF) activity. Administration of 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ), an inhibitor of PARP, decreased myocardial infarction size from 61.11+/-7.46%[0] to 38.83+/-5.67% (P<0.05) and cells apoptosis from 35+/-5.3% to 20+/-4.1% (P<0.05) and simultaneously improved the cardiac function. Western blot analysis showed that administration of DPQ 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. The results of the present study demonstrated that the inhibition of PARP was able to reduce heart I/R injury in vivo. Our results also suggested that 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.
Song
Zhao-Feng
ZF
Department of Cardiology, Shandong University Qilu Hospital, Jinan, Shandong Province, China.
Ji
Xiao-Ping
XP
Li
Xiao-Xing
XX
Wang
Sheng-Jun
SJ
Wang
Shu-Hua
SH
Zhang
Yun
Y
D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D015153:Blotting, Western; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D006334:Heart Function Tests; D020287:In Situ Nick-End Labeling; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar
D051033:Apoptosis Inducing Factor; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases
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