Angiotensin 1-7 Decreases Skeletal Muscle Atrophy induced by Angiotensin II through Mas Receptor Dependent Mechanism

Skeletal muscle atrophy is a pathological condition characterized by the loss of strength and muscle mass, increase in myosin heavy chain (MHC) degradation, and the increase in the expression of two muscle-specific ubiquitin ligases: atrogin-1 and MuRF-1. Angiotensin II (AngII) induces muscle atrophy. Angiotensin 1-7 (Ang (1-7)), through its receptor Mas, produces the opposite effects than AngII. We assessed the effects of Ang (1-7) on the skeletal muscle atrophy induced by AngII. Our results shows that Ang (1-7), through Mas, prevents the effects induced by AngII in muscle gastrocnemius: the decrease in the fibre diameter, muscle strength and MHC levels, and the increase in atrogin-1 and MuRF-1. Ang (1-7) also induces AKT phosphorylation. In addition, our analysis in vitro using C2C12 myotubes show that Ang (1-7), through a mechanism dependent on Mas, prevents the decrease in the levels of MHC and the increase in the expression of the atrogin-1 and MuRF-1, both induced by AngII. Ang (1-7) induces AKT phosphorylation in myotubes; additionally, we demonstrated that the inhibition of AKT with MK-2206 decreases the anti-atrophic effects of Ang (1-7). Thus, we demonstrated for the first time that Ang (1-7) counteracts the skeletal muscle atrophy induced by AngII through a mechanism dependent on the Mas receptor, which involves AKT activity. Our study indicates that Ang (1-7) is novel molecule with a potential therapeutical use to improve muscle wasting associated, at least, t...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research