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

• Main Authors: Sabrina Conejeros-Lillo (Author), Francisco Aguirre (Author), Daniel Cabrera (Author), Felipe Simon (Author), Luis Peñailillo (Author), Claudio Cabello-Verrugio (Author)
• Format: Book
• Published: PAGEPress Publications, 2024-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.4081/ejtm.2024.12249; 2037-7452; 2037-7460
• Keywords: Irisin; saliva; serum; muscle; physical exercise; Medicine; R; Human anatomy; QM1-695
• Source: European Journal of Translational Myology (2024)

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.