The restoration of Wnt/β-catenin signalling activity by a tuna backbone-derived peptide ameliorates hypoxia-induced cardiomyocyte injury.

Myocardial infarction (MI) is a serious disease with high morbidity and mortality worldwide. Reducing myocardial reperfusion injury in MI patients remains a challenge. The generation of excessive reactive oxygen species (ROS) during reperfusion is known to be responsible for injury. A peptide from tuna backbone protein (APTBP) captured our attention due to its strong antioxidant activity. Here, we aimed to assess the function of APTBP in protecting against myocardial ischaemia-reperfusion (I/R) injury and to clarify the associated mechanism. Two in vitro models generated by hypoxia and cobalt chloride treatment were used to determine the effect of APTBP on cardiomyocytes under hypoxic stress. In vivo, a rat model of I/R was generated to evaluate APTBP functions. As a result, APTBP attenuated hypoxia- or cobalt chloride-induced injury to H9C2 cells and primary cardiomyocytes. Moreover, hypoxia-induced apoptosis, ROS generation and impaired mitochondrial function were also suppressed by APTBP administration. In vivo, tail vein injection of APTBP ameliorated pathological damage and mildly restored cardiac function. To clarify the mechanism, RNA-seq was performed and revealed that the Wnt signalling pathway may be associated with this mechanism. Rescue analysis showed that β-catenin knockdown diminished the protective effect of APTBP and that the expression of an ROS generator abolished the restoration of Wnt/β-catenin signalling induced by APTBP. Collectively, our findings suggest that APTBP reduces cardiomyocyte apoptosis and protects against myocardial ischaemia-reperfusion injury by scavenging ROS and subsequently restoring Wnt/β-catenin signalling.