Poly (ADP-ribose) polymerase contributes myocardial ischemia-reperfusion of rats by regulating Akt signaling pathway.
- Author:
Zhao-feng SONG
1
Author Information
- Publication Type:Journal Article
- MeSH: 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
- From: Chinese Journal of Cardiology 2013;41(2):156-160
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODRats 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).
CONCLUSIONPARP activation contributes to myocardial I/R injury in rats by modulating Akt mediated signaling pathway.
