Evolution of β-catenin-independent Wnt-GSK3-mTOR signalling in regulation of energy metabolism in isoproterenol-induced cardiotoxicity model

Objective Isoproterenol (ISO) is widely used agent to study the effects of interventions which could prevent or attenuate the development of myocardial infarction. The sequence of pathological event's revealed that increased myocardial tissue oxygen demand and energy dysregulation exist early during Iso-induced cardiac toxicity. Later, tissue hypoxia results in increased oxidative stress, inflammation and fibrosis along with cardiac dysfunction in this model. The canonical Wnt/beta-catenin pathway has been reported to directly implicate in inducing cardiomyocyte hypertrophy and remodelling. However, less is known about the role of non-canonical Wnt signalling in cardiac diseases. Method Certain evidences have suggested that the activation of Wnt could up-regulate key energy sensor and cell growth regulator mTOR (Mechanistic target of rapamycin) by inhibition of GSK-3 beta mediator. Result The GSK-3 beta could negatively influence the mTOR activity and produce energy dysregulation during stress or hypoxic conditions. This suggests that the inhibition of GSK-3 beta by Wnt signalling could up-regulate mTOR levels and thereby restore early myocardial tissue energy balance and prevent cardiac toxicity in rodents. Conclusion We hereby discuss a novel therapeutic role of the beta-catenin independent, Wnt-GSK3-mTOR axis in attenuation of Iso-induced cardiotoxicity in rodents.

Automated summary

Research shows that the activation of Wnt could up-regulate key energy sensor and cell growth regulator mTOR by inhibiting the GSK-3 beta mediator. GSK-3 beta negatively influences mTOR activity under stress or hypoxic conditions, leading to energy dysregulation. Therefore, inhibiting GSK-3 beta by Wnt signaling may up-regulate mTOR levels and restore early myocardial tissue energy balance to prevent cardiac toxicity in rodents.