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

Eur J Transl Myol

Laboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Life Sciences, Universidad Andres Bello, Santiago.

Published: February 2024

AI Article Synopsis

  • * The study investigated how the protein CCL5/RANTES affects the components of the UPS and its role in causing a sarcopenic-like effect in muscle cells.
  • * Findings showed that CCL5 increases levels of MuRF-1 and atrogin-1, as well as certain proteasome subunits, while the MG132 inhibitor helped mitigate muscle loss, indicating CCL5's significant influence on the UPS and its contribution to muscle degradation.

Article Abstract

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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11017164PMC
http://dx.doi.org/10.4081/ejtm.2024.12249DOI Listing

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