Abstract
Objectives
Autophagy is a physiological and highly regulated mechanism, crucial for cell homeostasis maintenance. Its impairment seems to be involved in the onset of several diseases, including muscular dystrophies, myopathies and sarcopenia. According to few papers, chemotherapeutic drug treatment is able to trigger side effects on skeletal muscle tissue and, among these, a defective autophagic activation, which leads to the persistence of abnormal organelles within cells and, finally, to myofiber degeneration. The aim of this work is to find a strategy, based on diet modulation, to prevent etoposide-induced damage, in a model of in vitro skeletal muscle cells.
Methods
Glutamine supplementation and nutrient deprivation have been chosen as pre-treatments to counteract etoposide effect, a chemotherapeutic drug known to induce oxidative stress and cell death. Cell response has been evaluated by means of morpho-functional, cytofluorimetric and molecular analyses.
Results
Etoposide treated cells, if compared to control, showed dysfunctional mitochondria presence, ER stress and lysosomal compartment damage, confirmed by molecular investigations.
Conclusions
Interestingly, both dietary approaches were able to rescue myofiber from etoposide-induced damage. Glutamine supplementation, in particular, seemed to be a good strategy to preserve cell ultrastructure and functionality, by preventing the autophagic impairment and partially restoring the normal lysosomal activity, thus maintaining skeletal muscle homeostasis.
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References
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Acknowledgments
This work has been possible thanks to the DISB 2017 Enhancement Project of Urbino University. We would like to thank the researchers of the Translational Cardiomyology Laboratory (KU Leuven) for suggestions and support in IF analyses.
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Giordano, F.M., Burattini, S., Buontempo, F. et al. Diet Modulation Restores Autophagic Flux in Damaged Skeletal Muscle Cells. J Nutr Health Aging 23, 739–745 (2019). https://doi.org/10.1007/s12603-019-1245-3
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DOI: https://doi.org/10.1007/s12603-019-1245-3