Phosphatidylinositol-3-kinase signaling is required for erythropoietin-mediated acute protection against myocardial ischemia/reperfusion injury.
BACKGROUND
Parenteral administration of recombinant human erythropoietin (rhEPO) to rats induces protection against myocardial ischemia/reperfusion injury 24 hours later. However, the mechanisms by which rhEPO mediates protection have not been determined.


RESULTS
rhEPO was perfused into isolated rat hearts over 15 minutes immediately before 30 minutes of no-flow ischemia and 45 minutes of reperfusion. Compared with saline-perfused control hearts, recovery of left ventricular developed pressure was increased in rhEPO-perfused hearts. rhEPO also increased AKT activity and decreased apoptosis. All of these effects were blocked when the phosphatidylinositol-3-kinase inhibitor wortmannin was infused with rhEPO.


CONCLUSIONS
rhEPO provides immediate protection against ischemia/reperfusion injury in the isolated perfused rat heart that is mediated by the phosphatidylinositol-3-kinase pathway.
Cai
Zheqing
Z
Institute for Cell Engineering, McKusick-Nathans Institute of Genetic Medicine, and Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Md, USA.
Semenza
Gregg L
GL
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000187:drug effects*; D000077191:Wortmannin
D000730:Androstadienes; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D004921:Erythropoietin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins; D000077191:Wortmannin; C494920:Akt1 protein, rat