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‐1α) and mitochondrial membrane proteins, the inner membrane (Tim23), mitofusin 1 (Mfn1), and mitofusin 2 (Mfn2). RhNRG‐1 pretreatment effectively restored the expression of PGC‐1α 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.

中文翻译：

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Neuregulin-1促进线粒体生物发生，减轻线粒体功能障碍，并防止新生儿心肌细胞的缺氧/复氧损伤。

神经调节蛋白-1（NRG-1）/红细胞白血病病毒癌基因同源物（ErbB）途径的激活在调节成年心脏对生理和病理压力的适应性中起着至关重要的作用。在本研究中，我们研究了重组人NRG-1（rhNRG-1）对暴露于缺氧/复氧（H / R）的新生大鼠心脏心肌细胞（NRCM）中线粒体生物发生，线粒体功能和细胞存活的影响。这项研究的结果表明，在暴露于H / R的NRCM中，线粒体的生物发生受到损害，这表现为过氧化物酶体增殖物激活的受体γcoactivator-1α（PGC-1α）和线粒体膜蛋白的表达降低。 ，内膜（Tim23），mitofusin 1（Mfn1）和mitofusin 2（Mfn2）。RhNRG-1预处理有效地恢复了PGC-1α和这些膜蛋白的表达，上调了抗凋亡蛋白Bcl-2和Bcl-xL的表达，保留了线粒体膜电位，并减弱了H / R诱导的细胞凋亡。用siRNA阻断PGC-1的表达消除了rhNRG-1对线粒体功能和细胞存活的有益作用。本研究的结果有力地表明，NRG-1 / ErbB激活通过促进线粒体生物发生和改善线粒体内稳态，增强了心肌细胞对H / R损伤的适应性。用siRNA阻断PGC-1的表达消除了rhNRG-1对线粒体功能和细胞存活的有益作用。本研究的结果有力地表明，NRG-1 / ErbB激活通过促进线粒体生物发生和改善线粒体内稳态，增强了心肌细胞对H / R损伤的适应性。用siRNA阻断PGC-1的表达消除了rhNRG-1对线粒体功能和细胞存活的有益作用。本研究的结果有力地表明，NRG-1 / ErbB激活通过促进线粒体生物发生和改善线粒体内稳态，增强了心肌细胞对H / R损伤的适应性。