Phoenixin-14: detection and novel physiological implications in cardiac modulation and cardioprotection
Phoenixin-14: detection and novel physiological implications in cardiac modulation and cardioprotection
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DOI：
10.1007/s00018-017-2661-3
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发表时间：
2018-02-01
影响因子：
8
通讯作者：
Angelone, Tommaso
中科院分区：
文献类型：
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作者：
Rocca, C.;Scavello, F.;Angelone, Tommaso
Phoenixin-14 （PNX）是一种新发现的肽，在下丘脑与具有厌食性和心脏活性的Nesfatin-1共表达。像Nesfatin-1一样，PNX能够穿过血脑屏障，这表明在外周调节中起作用。初步的质谱数据表明，除了下丘脑，PNX也存在于哺乳动物的心脏中。本研究旨在量化PNX在大鼠心脏中的表达，并评估该肽在基础状态和缺血/再灌注（I/R）状态下是否影响心肌功能。ELISA法在下丘脑和心脏均检测到PNX的存在。在正常大鼠而非肥胖大鼠的血浆中，肽浓度在餐后升高。将分离的和Langendorff灌注的大鼠心脏暴露于外源性PNX诱导收缩性和舒张性降低，但对冠状动脉压力和心率没有影响。免疫印迹显示，这些作用伴随着Erk1/2、Akt和eNOS磷酸化的增加。PNX （EC50剂量），缺血后给予，诱导后适应样心脏保护。这表明，与仅暴露于I/R的心脏相比，梗死面积更小，收缩恢复更好。该肽还激活心脏保护的RISK和SAFE级联，并抑制细胞凋亡。在肥胖大鼠的心脏中也观察到这些影响。我们的数据提供了PNX外周活性的第一个证据，以及它在正常情况下和代谢紊乱情况下的直接心脏调节和心脏保护作用。
Phoenixin-14 (PNX) is a newly identified peptide co-expressed in the hypothalamus with the anorexic and cardioactive Nesfatin-1. Like Nesfatin-1, PNX is able to cross the blood-brain barrier and this suggests a role in peripheral modulation. Preliminary mass spectrography data indicate that, in addition to the hypothalamus, PNX is present in the mammalian heart. This study aimed to quantify PNX expression in the rat heart, and to evaluate whether the peptide influences the myocardial function under basal condition and in the presence of ischemia/reperfusion (I/R). By ELISA the presence of PNX was detected in both hypothalamus and heart. In plasma of normal, but not of obese rats, the peptide concentrations increased after meal. Exposure of the isolated and Langendorff perfused rat heart to exogenous PNX induces a reduction of contractility and relaxation, without effects on coronary pressure and heart rate. As revealed by immunoblotting, these effects were accompanied by an increase of Erk1/2, Akt and eNOS phosphorylation. PNX (EC50 dose), administered after ischemia, induced post-conditioning-like cardioprotection. This was revealed by a smaller infarct size and a better systolic recovery with respect to those detected on hearts exposed to I/R alone. The peptide also activates the cardioprotective RISK and SAFE cascades and inhibits apoptosis. These effects were also observed in the heart of obese rats. Our data provide a first evidence on the peripheral activity of PNX and on its direct cardiomodulatory and cardioprotective role under both normal conditions and in the presence of metabolic disorders.