Neuregulin-1 promotes mitochondrial biogenesis, attenuates mitochondrial dysfunction, and prevents hypoxia/reoxygenation injury in neonatal cardiomyocytes.
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. 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.
['Zhang|Xiao-Xia|XX|https://orcid.org/0000-0003-4872-3964', 'Wu|Xue-Si|XS|', 'Mi|Shu-Hua|SH|', 'Fang|Shan-Juan|SJ|', 'Liu|Sa|S|', 'Xin|Yi|Y|', 'Zhao|Quan-Ming|QM|']
D000818:Animals D015687:Cell Hypoxia D002470:Cell Survival D002478:Cells, Cultured D006801:Humans D008565:Membrane Proteins D008928:Mitochondria D032383:Myocytes, Cardiac D010100:Oxygen D051381:Rats D017207:Rats, Sprague-Dawley D011994:Recombinant Proteins
mitochondrial biogenesis hypoxia/reoxygenation cardiomyocytes apoptosis neuregulin