Erythropoietin protects cardiac myocytes from hypoxia-induced apoptosis through an Akt-dependent pathway

被引:241
作者
Tramontano, AF
Muniyappa, R
Black, AD
Blendea, MC
Cohen, I
Deng, LL
Sowers, JR
Cutaia, MV
El-Sherif, N
机构
[1] New York Harbor VA Care Syst, Brooklyn, NY 11209 USA
[2] Suny Downstate Med Ctr, Dept Med, Div Cardiovasc Med, Brooklyn, NY 11203 USA
[3] Suny Downstate Med Ctr, Dept Med, Div Endocrinol, Brooklyn, NY 11203 USA
[4] Suny Downstate Med Ctr, Dept Med, Div Pulmonol, Brooklyn, NY 11203 USA
关键词
apoptosis; erythropoietin; hypoxia; neonatal cardiomyocyte;
D O I
10.1016/S0006-291X(03)01503-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:990 / 994
页数:5
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