Erythropoietin protects cardiac myocytes from hypoxia-induced apoptosis through an Akt-dependent pathway.
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.
Tramontano
Anthony F
AF
The New York Harbor VA Health Care System, Brooklyn Campus, and Department of Medicine, State University of New York, Downstate Medical Center, USA. antoniotramontano@hotmail.com
Muniyappa
Ranganath
R
Black
Aislinn D
AD
Blendea
Mihaela C
MC
Cohen
Inna
I
Deng
Lili
L
Sowers
James R
JR
Cutaia
Michael V
MV
El-Sherif
Nabil
N
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases / Q000378:metabolism; D004921:Erythropoietin / Q000378:metabolism / Q000502:physiology*; D005434:Flow Cytometry; D006352:Heart Ventricles / Q000166:cytology; D000860:Hypoxia; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D017202:Myocardial Ischemia; D009206:Myocardium / Q000166:cytology* / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D017467:Receptors, Erythropoietin / Q000502:physiology
D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases; D004921:Erythropoietin; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D017467:Receptors, Erythropoietin; C494920:Akt1 protein, rat; C505407:CASP3 protein, human; C505520:CASP7 protein, human; C505410:Casp3 protein, rat