Tsang, A and Hausenloy, DJ and Mocanu, MM and Yellon, DM (2004) Postconditioning: A form of "modified reperfusion" protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway. CIRC RES , 95 (3) 230 - 232. 10.1161/01.RES.0000138303.76488.fe.
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Brief intermittent episodes of ischemia and reperfusion, at the onset of reperfusion after a prolonged period of ischemia, confer cardioprotection, a phenomenon termed "ischemic postconditioning" (Postcond). We hypothesized that this phenomenon may just represent a modified form of reperfusion that activates the reperfusion injury salvage kinase ( RISK) pathway. Isolated perfused rat hearts were subjected to: (a) 35 minutes of ischemia and 120 minutes of reperfusion, and infarct size was determined by tetrazolium staining; or (b) 35 minutes of ischemia and 7 minutes of reperfusion, and the phosphorylation states of Akt, endothelial NO synthase (eNOS), and p70S6K were determined. Postcond reduced infarct size from 51.2 +/- 3.4% to 31.5 +/- 4.1% (P < 0.01), an effect comparable with ischemic preconditioning (IPC; 27.5 +/- 2.3%; P < 0.01). Of interest, the combined protective effects of IPC and Postcond were not additive (30.1 +/- 4.8% with IPC+ Postcond; P = NS). Inhibiting phosphatidylinositol 3-kinase (PI3K) at reperfusion using LY or Wortmannin ( Wort) during the first 15 minutes of reperfusion completely abolished Postcond-induced protection (31.5 +/- 4.1% with Postcond versus 51.7 +/- 4.5% with Postcond + LY, P < 0.01; 56.2 +/- 10.1% with Postcond + Wort; P < 0.01), suggesting that Postcond protects the heart by activating PI3K-Akt. Western blot analysis demonstrated that Postcond induced a significant increase in phosphorylation of Akt, eNOS, and p70S6K in an LY- and Wort-sensitive manner. In conclusion, we show for the first time that ischemic Postcond protects the myocardium by activating the prosurvival kinases PI3K-Akt, eNOS, and p70S6K in accordance with the RISK pathway.
|Title:||Postconditioning: A form of "modified reperfusion" protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway|
|Keywords:||ischemia, cardioprotection, reperfusion, postconditioning, kinases, MITOCHONDRIAL PERMEABILITY TRANSITION, NITRIC-OXIDE, INJURY, ISCHEMIA, KINASE|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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