Cell Death Diff：神经营养素是保护心脏的天然蛋白质

生物谷报道：以前我们知道，心脏损伤的保护都与心脏中相关的因子有关，如VEGF，ET等，神经损伤与修复则是与神经因子有关，但最近英国一项最新研究表明，神经营养素Neurotrophins (NTs)不仅对神经细胞起作用外，还能在心脏冠状动脉发生阻塞时提高心脏细胞的存活率。这篇报道发表在Nature系列期刊Cell Death Diff 11月份杂志上，由英国The Bristol Heart Institute和意大利科学家共同发现的成果。

 

     如果向心脏供血的冠状动脉因胆固醇过高而发生阻塞，相关区域的心脏细胞会大量死亡，并可能导致心力衰竭。老鼠实验显示，将“NT”注入实验鼠心脏的“死亡区域”，相关细胞的存活率会大幅上升。

 

这项研究的负责人科斯坦扎·埃马努埃利说：“这是首次发现‘NT’对心脏有积极作用。利用这种物质，未来有可能开发出保护心脏的新方法。”

生物谷评论认为，人体内许多营养因子具有泛保护特征，这种例子在以前也发现过很多。如许多神经肽对胃肠和心脏具有保护作用，如CGRP（降钙素基因相关肽），VIP（血管活性肠肽）等，虽然是神经肽，但具有保护心脏和胃肠的作用。同时，神经因子的功能也越来越不局限于神经方面，如神经因子对免疫系统的调节作用，也是近年来的重要发现，这些研究表明，人体是复杂的，这些因子的调控远比我们想象的复杂得多，值得科学家更深入地探索。

Neurotrophins (NTs) control neuron survival and regeneration. Recent research showed that NTs possess cardiovascular actions. In this study, we investigated the hypothesis that the NT nerve growth factor (NGF) prevents cardiomyocyte apoptosis. We demonstrated that cultured rat neonatal cardiomyocytes (RNCMs) produce NGF and express its trkA (tropomyosin-related receptor A (NGF high-affinity receptor)) receptor. RNCMs given a neutralizing antibody for NGF or the trkA inhibitor K252a underwent apoptosis, thus suggesting that NGF is an endogenous prosurvival factor for cardiomyocytes. Adenovirus (Ad)-mediated NGF overexpression protected RNCMs from apoptosis induced by either hypoxia/reoxygenation or angiotensin II (AngII). Similarly, recombinant NGF inhibited AngII-induced apoptosis in isolated rat adult cardiomyocytes. Finally, in a rat model of myocardial infarction, NGF gene transfer promoted cardiomyocyte survival. In RNCMs, recombinant NGF induced trkA phosphorylation, followed by Ser473 phosphorylation and nuclear translocation of phospho-protein kinase B (Akt). In response to Akt activation, Forkhead transcription factors Foxo-3a and Foxo-1 were phosphorylated and excluded from the nucleus. The prosurvival effect of adenoviral vector carrying the human NGF gene was inhibited in vitro by K252a, LY294002 (a pan-phosphatidyl inositol 3-kinase – PI3K – inhibitor), an Akt small interfering RNA, and adenoviruses carrying a dominant negative mutant form of Akt (Ad.DN.Akt) or an Akt-resistant Foxo-3a (Ad.AAA-Foxo-3a). These results newly demonstrate the cardiac prosurvival action of NGF and provide mechanistic information on the signaling pathway, which encompasses trkA, PI3K-Akt, and Foxo.

原始出处：

Cell Death and Differentiation advance online publication 9 November 2007; doi: 10.1038/sj.cdd.4402263
Identification of the prosurvival activity of nerve growth factor on cardiac myocytes.

A Caporali¹, G B Sala-Newby¹, M Meloni¹, G Graiani², E Pani¹, B Cristofaro¹, A C Newby¹, P Madeddu¹ and C Emanueli¹