Poly (ADP-ribose) polymerase inhibitor reduces heart ischaemia/reperfusion injury via inflammation and Akt signalling in rats
Song Zhao-feng; Chen Dong-yu; Du Bo; Ji Xiao-ping
| HERO ID | 4854495 |
|---|---|
| In Press | No |
| Year | 2013 |
| Title | Poly (ADP-ribose) polymerase inhibitor reduces heart ischaemia/reperfusion injury via inflammation and Akt signalling in rats |
| Authors | Song Zhao-feng; Chen Dong-yu; Du Bo; Ji Xiao-ping |
| Journal | Chinese Medical Journal |
| Volume | 126 |
| Issue | 10 |
| Page Numbers | 1913-1917 |
| Abstract | Background Poly (ADP-ribose) polymerase (PARP) has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion (I/R) injury. 3,4-dihydro-5[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ), a potent PARP inhibitor, has cardiac protective effects. Because the underlying mechanisms are not understood, we investigated the effect of DPQ on heart I/R injury and its mechanisms. <br> <br>Methods Studies were performed with I/R rats' hearts. DPQ was used to inhibit the activation of PARP. Cardiac function and cellular apoptosis were assessed. The activation of PARP, transcription factor nuclear factor-kappaB (NF-KB), intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) were evaluated. We also evaluated expression of Akt and two of its downstream targets, glycogen synthase kinase-3 beta (GSK-3 beta) and forkhead transcription factor FOX03a. <br> <br>Results Administration of DPQ significantly decreased the activation of PARP and cellular apoptosis from (35 +/- 5)% to (20 +/- 4)% and simultaneously improved the cardiac function. DPQ reduced the expressions of NF-kappa B, ICAM-1, COX-2 and MMP-9 in rat heart and facilitated the activations of phosphor-Akt, phosphor-GSK-313 and phosphor-FOX03a. <br> <br>Conclusion The protective effects of DPQ were associated with the suppression of inflammation and the activation of the Akt signalling pathways suggesting that the inhibition of poly (ADP-ribose) polymerase reduced heart I/R injury in rats. |
| Doi | 10.3760/cma.j.issn.0366-6999.20121234 |
| Pmid | 23673109 |
| Wosid | WOS:000319529200021 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | heart ischaemia/reperfusion; poly (ADP-ribose) polymerase; 3,4-dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone; Akt; inflammation |