Erythropoietin protects cardiac myocytes from hypoxia-induced apoptosis through an Akt-dependent pathway
Abstract
Apoptosis is a contributing cause of myocyte loss in ischemic heart disease. Recent work has shown that erythropoietin (EPO) offers protection against apoptosis in a wide variety of tissues. We demonstrate that the erythropoietin receptor (EPOR) is expressed in the neonatal rat ventricular myocyte (NRVM). Exposure of NRVMs to hypoxia, with recombinant human EPO, significantly decreased apoptosis as measured by TUNEL, flow cytometry, and caspase 3/7 like activity when compared to hypoxia treatment alone. EPO administered at the initiation of coronary artery occlusion in the rat significantly decreased apoptosis in the myocardial ischemic region. In the NRVM, EPO increased the activity of Akt. The anti-apoptotic effect of EPO was abrogated by co-treatment with LY294002, a specific blocker of phosphatidylinositol 3-kinase (PI3-K). Our study demonstrates that EPO inhibits apoptosis in the NRVM exposed to hypoxia, through an Akt-dependent pathway. EPO also inhibits apoptosis in the in vivo rat model of myocardial ischemia.
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Cited By (7)
- Erythropoietin is neuroprotective, improves functional recovery, and reduces neuronal apoptosis and inflammation in a rodent model of experimental closed head injuryThe FASEB Journal · 2005
- Erythropoietin protects CA1 neurons against global cerebral ischemia in rat: potential signaling mechanismsJournal of Neuroscience Research · 2006
- The role of erythropoietin in myocardial protection: potential mechanisms and applicationsExpert Review of Cardiovascular Therapy · 2006
- Beneficial and ominous aspects of the pleiotropic action of erythropoietinAnnals of Hematology · 2004
- An update on the cardiac effects of erythropoietin cardioprotection by erythropoietin and the lessons learnt from studies in neuroprotectionCardiovascular Research · 2004
- Erythropoietin: novel approaches to neuroprotection in human brain diseaseMetabolic Brain Disease · 2004
- Erythropoietin on a tightrope: balancing neuronal and vascular protection between intrinsic and extrinsic pathways
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