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Peptides v.88, 2017년, pp.196 - 207   SCI SCIE
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Inhibition of endoplasmic reticulum stress by neuregulin-1 protects against myocardial ischemia/reperfusion injury

Fang, Shan-Juan (Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China ); Li, Peng-Yang (Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, No. 38, Xueyuan Road, Haidian District, Beijing 100191, China ); Wang, Chun-Mei (Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China ); Xin, Yi (Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China ); Lu, Wei-Wei (Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, No. 38, Xueyuan Road, Haidian District, Beijing 100191, China ); Zhang, Xiao-Xia (Emergency ); Zuo, Song ( ); Ma, Chang-Sheng ( ); Tang, Chao-Shu ( ); Nie, Shao-Ping ( ); Qi, Yong-Fen ( );
  • 초록  

    Abstract Neuregulin-1 (NRG-1), an endogenously produced polypeptide, is the ligand of cardiomyocyte ErbB receptors, with cardiovascular protective effects. In the present study, we explored whether the cardioprotective effect of NRG-1 against I/R injury is mediated by inhibiting myocardial endoplasmic reticulum (ER) stress. In vitro , NRG-1 directly inhibited the upregulation of ER stress markers such as glucose-regulated protein 78, CCAAT/enhancer binding protein homologous protein and cleaved caspase-12 induced by the ER stress inducers tunicamycin or dithiothreitol in both neonatal and adult ventricular myocytes. Attenuating ErbB signals by an ErbB inhibitor AG1478 or ErbB4 knockdown and preincubation with phosphoinositide 3-kinase inhibitors all reversed the effect of NRG-1 inhibiting ER stress in cultured neonatal rat cardiomyocytes. Concurrently, cardiomyocyte ER stress and apoptosis induced by hypoxia-reoxygenation were decreased by NRG-1 treatment in vitro . Furthermore, in an in vivo rat model of myocardium ischemia/reperfusion (I/R), intravenous NRG-1 administration significantly decreased ER stress and myocardial infarct size induced by I/R. NRG-1 could protect the heart against I/R injury by inhibiting myocardial ER stress, which might be mediated by the phosphoinositide 3-kinase/Akt signaling pathway. Highlights NRG-1 inhibits cardiomyocyte ER stress induced by tunicamycin and dithiothreitol. NRG-1 inhibits cardiomyocyte ER stress through ErbB4 receptor. The inhibitory effects of NRG-1 on cardiomyocyte ER stress is through PI3K/Akt signaling pathway. NRG-1 attenuates apoptosis and ER stress induced by H/R in cardiomyocytes. NRG-1 reduces the myocardial I/R injury and ER stress in I/R heart.


  • 주제어

    Neuregulin-1 .   Ischemia/reperfusion injury .   Endoplasmic reticulum stress .   Apoptosis .   Heart.  

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