[Poly (ADP-ribose) polymerase contributes myocardial ischemia-reperfusion of rats by regulating Akt signaling pathway].

Abstract

OBJECTIVE:

To investigate the effect of poly (ADP-ribose) polymerase (PARP) in heart ischemia and reperfusion (I/R) injury in rat and on Akt mediated signaling pathway.

METHOD:

Rats were divided into sham, I/R, I/R+3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)- isoquinolinone (DPQ, 10 mg/kg, i.p.), an inhibitor of PARP, I/R + DPQ + Akt inhibitor LY294002, 10 mg/kg (n = 12 each). Cardiac function, apoptosis of the cardiomyocytes were measured, myocardial expression of PARP, Akt, glycogen synthase kinase-3β (GSK-3β) and forkhead transcription factor FOXO3a were detected.

RESULTS:

(1) The expression of PARP were significantly upregulated in I/R group compared to sham group which was significantly attenuated in I/R + DPQ group (P < 0.05 vs. I/R group). (2)PARP inhibition significantly reduced cardiomyocyte apoptosis from (34.0 ± 6.2)% to (23.0 ± 3.8)% (P < 0.05). The LVDP, +dp/dt and -dp/dt were significantly higher in I/R + DPQ group compared to I/R group (all P < 0.05). (3) The expression of Akt, GSK-3β and FOXO3a were significantly upregulated in I/R + DPQ group compared to I/R group (P < 0.05) which were significantly attenuated in I/R + DPQ + LY294002 group compared to I/R + DPQ group (all P < 0.05).

CONCLUSION:

PARP activation contributes to myocardial I/R injury in rats by modulating Akt mediated signaling pathway.

• Authors: Zhao-feng Song
• Journal: Zhonghua xin xue guan bing za zhi (Zhonghua Xin Xue Guan Bing Za Zhi) Vol. 41 Issue 2 Pg. 156-60 (Feb 2013) ISSN: 0253-3758 [Print] China
• PMID: 23710748 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Poly(ADP-ribose) Polymerase Inhibitors
• Poly(ADP-ribose) Polymerases
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Disease Models, Animal
• Female
• Myocardial Reperfusion Injury (metabolism, physiopathology)
• Poly(ADP-ribose) Polymerase Inhibitors
• Poly(ADP-ribose) Polymerases (physiology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)