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GW23-e0509
INHIBITION OF THE ACTIVITY OF POLY (ADP-RIBOSE) POLYMERASE REDUCES HEART ISCHAEMIA/REPERFUSION INJURY VIA SUPPRESSING JNK MEDIATED AIF TRANSLOCATION
  1. Song Zhao-feng1,
  2. Chen Dong-yu2,
  3. Du Bo1,
  4. Ji Xiao-ping3,
  5. Song Zhao-feng1
  1. 1Department of Cardiology, Taian Central Hospital, 271000 Taian, Shandong Province, China
  2. 2Department of Rheumatology, Taian Central Hospital, 271000 Taian, Shandong Province, China
  3. 3Department of Cardiology, Shandong University Qilu Hospital, 250012 Jinan, Shandong Province, China

    Abstract

    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.

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