期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 296, 期 1, 页码 H84-H93出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00372.2008
关键词
myocyte; apoptosis; myocardial infarction; p38
资金
- Heart and Stroke Foundation of Ontario (HSFO) [T-6040]
- Ontario Graduate Scholarship Award
Burger D, Xiang F, Hammoud L, Lu X, Feng Q. Role of heme oxygenase-1 in the cardioprotective effects of erythropoietin during myocardial ischemia and reperfusion. Am J Physiol Heart Circ Physiol 296: H84-H93, 2009; doi: 10.1152/ajpheart.00372.2008. - We have recently demonstrated that erythropoietin (EPO) protects cardiomyocytes from apoptosis during myocardial ischemia-reperfusion (I/R). The objective of the present study was to investigate the role of heme oxygenase (HO)-1 in the antiapoptotic effects of EPO. Primary cultures of neonatal mouse cardiomyocytes were subjected to anoxia-reoxygenation (A/R). Pretreatment with EPO significantly reduced apoptosis in A/R-treated cells. This reduction in apoptosis was preceded by an increase in the mRNA and protein expression of HO-1. Selective inhibition of HO-1 using chromium mesoporphyrin (CrMP) significantly diminished the ability of EPO to inhibit apoptosis. Cotreatment of EPO with SB-202190, an inhibitor of p38 activation, blocked the EPO-mediated HO-1 expression and antiapoptotic effects, suggesting a p38-dependent mechanism. The in vivo significance of p38 and HO-1 as mediators of EPO's cardioprotection was investigated in mice subjected to myocardial I/R. Pretreatment with EPO decreased infarct size as well as I/R-induced apoptosis in wild-type mice. However, these effects were significantly diminished in HO-1(-/-) mice. Furthermore, EPO given during ischemia reduced infarct size in mice subjected to I/R, and this effect was blocked by CrMP treatment in wild-type mice. Moreover, inhibition of p38 diminished the cardioprotective effects of EPO. We conclude that upregulation of HO-1 expression via p38 signaling contributes to EPO-mediated cardioprotection during myocardial I/R.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据