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

Sabrina Conejeros-Lillo, Francisco Aguirre, Daniel Cabrera, Felipe Simon, Luis Peñailillo, Claudio Cabello-Verrugio*

*Autor correspondiente de este trabajo

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

Resumen

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 stopped the reduction in the diameter of single-isolated flexor digitorum brevis (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.

Idioma originalInglés
PublicaciónEuropean Journal of Translational Myology
Volumen34
N.º1
DOI
EstadoPublicada - 2024
Publicado de forma externa

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