Abstract

Myostatin is a myokine that regulates muscle function and mass, producing muscle atrophy. Myostatin induces the degradation of myofibrillar proteins, such as myosin heavy chain or troponin. The main pathway that mediates protein degradation during muscle atrophy is the ubiquitin proteasome system, by increasing the expression of atrogin-1 and MuRF-1. In addition, myostatin activates the NF-κB signaling pathway. Renin–angiotensin system (RAS) also regulates muscle mass. Angiotensin (1-7) (Ang-(1-7)) has anti-atrophic properties in skeletal muscle. In this paper, we evaluated the effect of Ang-(1-7) on muscle atrophy and signaling induced by myostatin. The results show that Ang-(1-7) prevented the decrease of the myotube diameter and myofibrillar protein levels induced by myostatin. Ang-(1-7) also abolished the increase of myostatin-induced reactive oxygen species production, atrogin-1, MuRF-1, and TNF-α gene expressions and NF-κB signaling activation. Ang-(1-7) inhibited the activity mediated by myostatin through Mas receptor, as is demonstrated by the loss of all Ang-(1-7)-induced effects when the Mas receptor antagonist A779 was used. Our results show that the effects of Ang-(1-7) on the myostatin-dependent muscle atrophy and signaling are blocked by MK-2206, an inhibitor of Akt/PKB. Together, these data indicate that Ang-(1-7) inhibited muscle atrophy and signaling induced by myostatin through a mechanism dependent on Mas receptor and Akt/PKB.

Highlights

  • Skeletal muscle atrophy is the loss of muscle mass and function [1,2]

  • This study demonstrates that Ang-(1-7), via the Mas receptor, can prevent myostatin-induced atrophy

  • This finding is supported by an in vitro analysis of the myostatin-dependent effect on the myotube diameter, myofibrillar protein levels, MuRF-1 gene expression, and reactive oxygen species (ROS) production, which were abolished by Ang-(1-7)

Read more

Summary

Introduction

Skeletal muscle atrophy is the loss of muscle mass and function [1,2]. Several causes that induce skeletal muscle atrophy include immobilization, sepsis, aging, or chronic diseases [2,3]. Some features of skeletal muscle atrophy include the decrease of muscle strength and fiber diameter, and the diminution of myofibrillar proteins, such as myosin heavy chain (MHC) and troponin [4,5]. The latter is produced by an unbalance between catabolic and anabolic mechanisms. The main protein catabolic pathway is the ubiquitin proteasome system (UPS), which is increased under atrophic conditions, as evidenced by an increase in the gene expression of two muscle-specific E3 ubiquitin ligases, atrogin-1/MAF-bx and MuRF-1/TRIM63 [6] These E3 ligases act for modifying MHC and troponin with ubiquitin [7]. Oxidative status is caused by an increase of reactive oxygen species (ROS) production and/or a decrease of the antioxidant mechanism in cells, which causes cellular damage [8]

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call