Reply to Abdelwahid and Smith: The effect on cardiomyocytes of helix B-surface peptide (HBSP), a peptide with cell-protective but not erythropoietic activities of erythropoietin
Reply to Abdelwahid and Smith: The effect on cardiomyocytes of helix B-surface peptide (HBSP), a peptide with cell-protective but not erythropoietic activities of erythropoietin
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回复 Abdelwahid 和 Smith：螺旋 B 表面肽 (HBSP) 对心肌细胞的影响，该肽具有细胞保护作用，但不具有促红细胞生成素的促红细胞生成活性
DOI：
10.1073/pnas.1012530108
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
and Cerami A
中科院分区：
文献类型：
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作者：
Kawakami M;Ueba H;Brines M;Yamin M;Umemoto T;Ako J;Momomura S;and Cerami A
我们怀着极大的兴趣阅读了Ueba等人最近在PNAS上发表的论文。(1)关于螺旋B-表面肽（HBSP）的心脏保护作用，HBSP是一种模拟促红细胞生成素3D结构的非促红细胞生成的组织保护肽。作者表明HBSP在体外和体内保护心肌细胞免于凋亡。论文中提出的HBSP的心肌保护是迷人的，并补充了其他关于促红细胞生成素（EPO）替代品的心肌细胞存活的工作。作者通过TUNEL和annexin V分析了HBSP对心肌细胞凋亡的影响。作者还试图分析HBSP在细胞存活中的信号转导。他们的结论是HBSP通过Akt依赖性途径保护心肌细胞免于凋亡并导致衰竭心脏的有利结果，这是生物学相关的。EPO已被证明在多种细胞类型中引起抗凋亡作用，包括心肌细胞（2）。此外，作者在他们的研究中使用TNF-α诱导细胞凋亡。TNF-α在缺血性损伤和炎症过程中在心脏中表达，并通过激活多种细胞死亡途径引起心肌细胞凋亡和心脏重塑。重要的是，半胱天冬酶激活在TNF-α诱导的细胞凋亡中起核心作用（3）。近年来，我们对心肌细胞中EPO应答的抗细胞凋亡细胞内信号传导事件的理解有了重大进展。这些努力需要继续，但重要的是使用适当的实验工具，提供与EPO和TNF-α的已知机制相关的答案。作者认为HBSP可替代EPO进行心脏保护的结论具有误导性，因为已知EPO可触发各种网络，包括JAK-STAT激活、Bcl-2、半胱天冬酶活性、蛋白激酶B（即Akt 1）和线粒体膜电位调节，以确保心肌细胞保护（4，5）。声称HBSP可以替代EPO在心脏保护中，进一步
We read with great interest the recent paper in PNAS by Ueba et al.(1) concerning the cardioprotection by helix B-surface peptide (HBSP), a nonerythropoietic, tissue-protective peptide mimicking the 3D structure of erythropoietin. The authors showed that HBSP protects cardiomyocytes from apoptosis in vitro and in vivo. Cardioprotection by HBSP presented in the paper was fascinating and complements other works concerning cardiomyocyte survival by erythropoietin (EPO) alternatives. The authors analyzed the effects of HBSP on cardiomyocyte apoptosis by using TUNEL and annexin V. The authors also attempted to analyze HBSP signaling in cell survival. Their conclusion that HBSP protects cardiomyocytes from apoptosis and leads to a favorable outcome in failing hearts through an Akt-dependent pathway is biologically relevant. EPO has been shown to cause antiapoptotic effects in a variety of cell types, including cardiomyocytes (2). In addition, the authors used TNF-α to induce apoptosis in their investigation. TNF-α is expressed in the heart during ischemic injury and inflammation and it provokes cardiomyocyte apoptosis and cardiac remodeling through activation of multiple cell death pathways. Importantly, caspase activation plays a central role in TNF-α–induced apoptosis (3).In recent years, there were significant advances in our understanding of antiapoptotic intracellular signaling events in response to EPO in cardiomyocytes. These efforts need to be continued, but it is important to use appropriate experimental tools that provide answers relevant for the known mechanisms of both EPO and TNF-α. The authors’ conclusion that HBSP can substitute EPO in cardioprotection is misleading, because EPO is known to trigger various networks including JAK-STAT activation, Bcl-2, caspase activity, protein kinase B (ie, Akt1), and modulation of mitochondrial membrane potential to ensure myocardial cytoprotection (4, 5). To claim that HBSP can substitute EPO in cardioprotection, further