title: ATP-induced cardioprotection against myocardial ischemia/reperfusion injury is mediated through the RISK pathway.
abstract: The aim of the present study was to examine the post-infarct acute effect of adenosine-5'-triphosphate (ATP) on myocardial infarction (MI) size as well as its precise molecular mechanism. Sixty New Zealand white male rabbits were exposed to 40 min of ischemia followed by 180 min of reperfusion. The rabbits were intravenously administered 3 mg/kg of ATP (ATP group) or saline (control group) immediately after reperfusion and maintained throughout the first 30 min. The wortmannin+ATP, PD-98059+ATP, and 5-hydroxydecanoic acid (5-HD) sodium salt+ATP groups were separately injected with wortmannin (0.6 mg/kg), PD-98059 (0.3 mg/kg), and 5-HD (5 mg/kg) 5 min prior to ATP administration. MI size was calculated as the percentage of the risk area in the left ventricle. Myocardial apoptosis was determined using a TUNEL assay. Western blot analysis was performed to examine the levels of protein kinase B (Akt)/p-Akt and extracellular signal-regulated kinase (ERK)/p-ERK in the ischemic myocardium, 180 min after reperfusion. The infarct size was significantly smaller in the ATP group than in the control group (p<0.05). The infarct size-reducing effect of ATP was completely blocked by wortmannin, PD-98059 and 5-HD. Compared with the control group, cardiomyocyte apoptosis was significantly reduced in the ATP group, while this did not occur in the wortmannin+ATP, PD-98059+ATP and 5-HD+ATP groups. Western blot analysis revealed a higher myocardial expression of p-Akt and p-ERK 180 min following reperfusion in the ATP versus the control group. In conclusion, cardioprotection by postischemic ATP administration is mediated through activation of the reperfusion injury salvage kinase (RISK) pathway and opening of the mitochondrial ATP-dependent potassium channels.
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
authors.forename: Zhe-Xun
authors.initials: ZX
authors.lastname: Lian
authors.affiliation: Department of Cardiology, The Third People's Hospital of Qingdao, Qingdao, Shandong 266000, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Interventional Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Fu
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
authors.forename: Zuo-Yuan
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xin
authors.affiliation: Department of Central Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
authors.forename: Ru-Yong
authors.initials: RY
authors.lastname: Yao
keywords: adenosine-5′-triphosphate; adenosine-5′-triphosphate-dependent potassium channels; myocardial reperfusion injury; reperfusion injury salvage kinase