Poly (ADP-ribose) polymerase inhibitor reduces heart ischaemia/reperfusion injury via inflammation and Akt signalling in rats.
- Author:
Zhao-Feng SONG
1
;
Dong-Yu CHEN
;
Bo DU
;
Xiao-Ping JI
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Blotting, Western; Enzyme Inhibitors; therapeutic use; Female; Isoquinolines; therapeutic use; Myocardial Reperfusion Injury; drug therapy; Piperidines; therapeutic use; Poly(ADP-ribose) Polymerase Inhibitors; Proto-Oncogene Proteins c-akt; metabolism; Rats; Rats, Wistar
- From: Chinese Medical Journal 2013;126(10):1913-1917
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDPoly (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.
METHODSStudies 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-κB), 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-3β (GSK-3β) and forkhead transcription factor FOXO3a.
RESULTSAdministration 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-κB, ICAM-1, COX-2 and MMP-9 in rat heart and facilitated the activations of phosphor-Akt, phosphor-GSK-3β and phosphor-FOXO3a.
CONCLUSIONThe 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.