Secretoneurin suppresses cardiac hypertrophy through suppression of oxidant stress
Secretoneurin suppresses cardiac hypertrophy through suppression of oxidant stress
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泌乳素通过抑制氧化应激来抑制心脏肥大
DOI：
10.1016/j.ejphar.2018.01.008
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发表时间：
2018-03-05
影响因子：
5
通讯作者：
Yu, Chao
中科院分区：
文献类型：
--
作者：
Chen, Hua-Li;Liu, Yan;Yu, Chao
神经肽分泌神经肽(SN)在心肌缺血中起保护作用。本研究旨在探讨SN在心肌肥厚中的作用。我们观察到，在异丙肾上腺素(ISO)诱导的心肌细胞肥大中，内源性SN在小鼠血浆、心肌和原代培养的心肌细胞中的表达显著增加。肥厚组小鼠心脏大小、心脏重量/体重(HW/BW)、心肌细胞大小、心钠素(ANP)和脑利钠肽(BNP)的表达均显著高于对照组，但SN基因治疗可有效抑制其表达。同样，在ISO处理后的培养心肌细胞中也观察到SN的保护作用。SN能显著提高心肌细胞过氧化氢酶和超氧化物歧化酶的活性，同时降低心肌细胞内的氧自由基水平。我们观察到SN可激活心肌细胞AMPK、P38/MAPK和ERK/MAPK通路，但仅用AMPK抑制剂(化合物C)和ERK1/2/MAPK抑制剂(PD98059)可拮抗SN对心肌细胞肥大的保护作用和对心肌细胞氧化应激的抑制作用。这些结果表明，内源性SN在肥大的心肌细胞中被诱导，并可能在心肌肥厚的发病机制中起到保护作用。这些结果提示，外源性SN可通过激活AMPK和ERK/MAPK通路，上调抗氧化剂，抑制氧化应激，从而保护ISO诱导的心肌肥大。
The neuropeptide secretoneurin (SN) plays protective roles in myocardial ischemia. In the present study, the effect of SN in cardiac hypertrophy was investigated. We observed that, in isoproterenol (ISO) treatment induced cardiac or cardiomyocytes hypertrophy, a marked increase in the expression of endogenous SN in mouse plasma, myocardium and primary-cultured cardiomyocytes occurs. In hypertrophic mice, the heart size, heart weight/body weight (HW/BW) ratio, cardiomyocyte size, and atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) expression were significantly higher than those in controls but were effectively suppressed by SN gene therapy. Similarly, the protective effects of SN were also observed in cultured cardiomyocytes following ISO treatment. SN significantly increased the activity of catalase and superoxide dismutase (SOD) in parallel with the decrease in reactive oxygen species levels in cardiomyocytes. We observed that SN evoked the activation of all of the AMPK, P38/MAPK and ERK/MAPK pathways in cardiomyocytes, but pretreatment with only AMPK inhibitor (compound C) and ERK1/2/MAPK inhibitor (PD98059) counteracted the protective effects of SN against cardiomyocyte hypertrophy and the suppressive effects of SN on oxidant stress in cardiomyocytes. These results indicated that endogenous SN is induced in hypertrophic cardiomyocytes, and may play a protective role in the pathogenesis of cardiac hypertrophy. These results suggest that exogenous SN supplementation protects the cardiac hypertrophy induced by ISO treatment through the activation of AMPK and ERK/MAPK pathways, thus upregulating antioxidants and suppressing oxidative stress.