ROLE OF THE UBIQUITIN-PROTEASOME SYSTEM IN THE SARCOPENIC-LIKE PHENOTYPE INDUCED BY CCL5/RANTES

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

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

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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 Diabetes Care 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 WILD BLUEBERRY SPREAD 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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