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

Abstract

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 StudyThe 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.

The involvement of Neuregulin-1 in the process of facial nerve injury repair through the utilization of dental pulp stem cells

“…Previous studies have demonstrated the inhibitory effects of NRG-1 on fibrosis [ 25 ], as well as its capacity to resist cellular senescence [ 21 ] and apoptosis [ 26 ]. Moreover, NRG-1 has been observed to mitigate mitochondrial dysfunction [ 22 ], stimulate cell proliferation and migration [ 27 ], induce differentiation [ 28 , 29 ], promote angiogenesis [ 22 ], and exhibit neuroprotective properties.…”

Neuregulin, an Effector on Mitochondria Metabolism That Preserves Insulin Sensitivity

“…Recent evidences support this view. In neonatal cardiomyocytes, submitted to hypoxia/reoxygenation injury, Hrg contributes to cardiomyocytes survival by restoring the expression of MFN1 and MFN2 (Zhang et al, 2020). All together suggest that NRG-1 has a prevalent role in muscle adaptation to an oxidative metabolism.…”

Role of the Mitochondrial Protein Import Machinery and Protein Processing in Heart Disease

“…Tim23 , the channel-forming protein of the TIM23 complex, responsible for the translocation of presequence precursors into mitochondrial matrix or IM, was reduced by hypoxia/reoxygenation (H/R) or I/R ( 207 , 242 , 243 ). Restoring expression of Tim23 by various treatments seemed protective ( 207 , 242 , 243 ) against H/R or I/R injuries.…”

“…Tim23 , the channel-forming protein of the TIM23 complex, responsible for the translocation of presequence precursors into mitochondrial matrix or IM, was reduced by hypoxia/reoxygenation (H/R) or I/R ( 207 , 242 , 243 ). Restoring expression of Tim23 by various treatments seemed protective ( 207 , 242 , 243 ) against H/R or I/R injuries. However, a controversial study from Bian showed that the protective role of zinc against I/R injury was mediated by enhanced mitophagy, accompanied by downregulation of Tom20 and Tim23 expression ( 244 ).…”