Role of the ubiquitin-proteasome system in the sarcopenic-like phenotype induced by CCL5/RANTES

Submitted: 31 December 2023
Accepted: 1 February 2024
Published: 15 February 2024
Abstract Views: 2299
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Sarcopenia is characterized by reduced muscle strength and mass and a decline in muscle fiber diameter and amount of sarcomeric proteins. Sarcopenia involves the activation of the ubiquitin-proteasome system (UPS). MuRF-1 and atrogin-1 are E3 ubiquitin ligases belonging to UPS, leading to proteolysis mediated by the PSMB 5, 6, and 7 subunits of 20S proteasome. CCL5/RANTES induces a sarcopenic-like effect in muscle cells. The present work explored the impact of CCL5 on UPS components and the influence of UPS on its sarcopenic-like effect. We demonstrated that CCL5 increased MuRF-1 and atrogin-1 protein levels and mRNA levels of subunits PSMB 5, 6, and 7. We used the MG132 inhibitor to elucidate the role of the 20S proteasome in the CCL5-induced sarcopenic-like effect. This inhibitor prevented the decrease in troponin and MHC protein levels and partially prevented the reduction in the diameter of single-isolated FDB muscle fibers induced by CCL5. These findings indicate that CCL5 actively modulates the UPS. Moreover, our results show the direct participation of UPS in the sarcopenic-like phenotype induced by CCL5.

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How to Cite

Conejeros-Lillo, S., Aguirre, F., Cabrera, D., Simon, F., Peñailillo, L., & Cabello-Verrugio, C. (2024). Role of the ubiquitin-proteasome system in the sarcopenic-like phenotype induced by CCL5/RANTES. European Journal of Translational Myology, 34(1). https://doi.org/10.4081/ejtm.2024.12249

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