Poly (ADP-ribose) polymerase inhibitor reduces heart ischaemia/reperfusion injury via inflammation and Akt signalling in rats.

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.

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-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.

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-κB, ICAM-1, COX-2 and MMP-9 in rat heart and facilitated the activations of phosphor-Akt, phosphor-GSK-3β and phosphor-FOXO3a.

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.

• Authors: Zhao-Feng Song, Dong-Yu Chen, Bo DU, Xiao-Ping Ji
• Journal: Chinese medical journal (Chin Med J (Engl)) Vol. 126 Issue 10 Pg. 1913-7 ( 2013) ISSN: 2542-5641 [Electronic] China
• PMID: 23673109 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Isoquinolines
• Piperidines
• Poly(ADP-ribose) Polymerase Inhibitors
• 3,4-dihydro-5-(4-(1-piperidinyl)butoxy)-1(2H)-isoquinolinone
• Proto-Oncogene Proteins c-akt

Topics

• 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