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

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Abstract

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/β-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-3β mediator.

Result

The GSK-3β could negatively influence the mTOR activity and produce energy dysregulation during stress or hypoxic conditions. This suggests that the inhibition of GSK-3β 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 β-catenin independent, Wnt–GSK3–mTOR axis in attenuation of Iso-induced cardiotoxicity in rodents.

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Acknowledgements

Authors thank Mr. Parveen Garg, Chairman ISF College of Pharmacy, Moga, India for providing necessary facilities for completion of this work.

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Authors and Affiliations

  1. Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India

    Shriyansh Srivastava, Newly Bagang, Shubham Yadav, Sakshi Rajput, Divya Sharma, Ashish Dahiya, Loveinder Bhardwaj, Khalid Deshmukh & Gaaminepreet Singh

  2. Department of Pharmacology, College of Medicine, University of Illinios, Chicago, USA

    Jagdish Chandra Joshi

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  1. Shriyansh Srivastava
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Srivastava, S., Bagang, N., Yadav, S. et al. Evolution of β-catenin-independent Wnt–GSK3–mTOR signalling in regulation of energy metabolism in isoproterenol-induced cardiotoxicity model. Inflamm. Res. 70, 743–747 (2021). https://doi.org/10.1007/s00011-021-01477-8

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  • DOI: https://doi.org/10.1007/s00011-021-01477-8

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