Neuregulin-1 promotes mitochondrial biogenesis, attenuates mitochondrial dysfunction, and prevents hypoxia/reoxygenation injury in neonatal cardiomyocytes

被引:11
作者
Zhang, Xiao-Xia [1 ]
Wu, Xue-Si [1 ]
Mi, Shu-Hua [1 ]
Fang, Shan-Juan [2 ]
Liu, Sa [3 ]
Xin, Yi [3 ]
Zhao, Quan-Ming [1 ]
机构
[1] Capital Med Univ, Beijing AnZhen Hosp, Dept Cardiol, Beijing 100029, Peoples R China
[2] Capital Med Univ, Beijing Anzhen Hosp, Emergency & Crit Care Ctr, Beijing, Peoples R China
[3] Capital Med Univ, Beijing Anzhen Hosp, Inst Heart Lung & Blood Vessel Dis, Beijing, Peoples R China
基金
中国国家自然科学基金;
关键词
apoptosis; cardiomyocytes; hypoxia; reoxygenation; mitochondrial biogenesis; neuregulin; ISCHEMIA-REPERFUSION INJURY; ISCHEMIA/REPERFUSION-INJURY; CELL-DEATH; CARDIAC MYOCYTES; PROTECTS; APOPTOSIS; HEART; ERBB2; TRANSCRIPTION; INHIBITION;
D O I
10.1002/cbf.3503
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Neuregulin-1 (NRG-1)/erythroblastic leukaemia viral oncogene homologues (ErbB) pathway activation plays a crucial role in regulating the adaptation of the adult heart to physiological and pathological stress. In the present study, we investigate the effect of recombined human NRG-1 (rhNRG-1) on mitochondrial biogenesis, mitochondrial function, and cell survival in neonatal rat cardiac myocytes (NRCMs) exposed to hypoxia/reoxygenation (H/R). The results of this study showed that, in the H/R-exposed NRCMs, mitochondrial biogenesis was impaired, as manifested by the decrease of the expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) and mitochondrial membrane proteins, the inner membrane (Tim23), mitofusin 1 (Mfn1), and mitofusin 2 (Mfn2). RhNRG-1 pretreatment effectively restored the expression of PGC-1 alpha and these membrane proteins, upregulated the expression of the anti-apoptosis proteins Bcl-2 and Bcl-xL, preserved the mitochondrial membrane potential, and attenuated H/R-induced cell apoptosis. Blocking PGC-1 expression with siRNA abolished the beneficial role of rhNRG-1 on mitochondrial function and cell survival. The results of the present study strongly suggest that NRG-1/ErbB activation enhances the adaption of cardiomyocytes to H/R injury via promoted mitochondrial biogenesis and improved mitochondrial homeostasis. Significance of the Study The results of this research revealed for the first time the relationship between neuregulin-1 (NRG-1)/erythroblastic leukaemia viral oncogene homologues (ErbB) activation and mitochondrial biogenesis in neonatal cardiomyocytes and verified the significance of this promoted mitochondrial biogenesis in attenuating hypoxia/reoxygenation injury. This finding may open a new field to further understand the biological role of NRG-1/ErbB signalling pathway in cardiomyocyte.
引用
收藏
页码:549 / 557
页数:9
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