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Pflugers Arch. 2015 Sep;467(9):1975-84. doi: 10.1007/s00424-014-1617-9. Epub 2014 Oct 9.

The angiotensin-(1-7)/Mas axis reduces myonuclear apoptosis during recovery from angiotensin II-induced skeletal muscle atrophy in mice.

Author information

1
Laboratorio de Biología y Fisiopatología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andres Bello, Santiago, Chile.

Abstract

Angiotensin-(1-7) [Ang (1-7)] is a peptide belonging to the non-classical renin-angiotensin system (RAS). Ang (1-7), through its receptor Mas, has an opposite action to angiotensin II (Ang II), the typical peptide of the classical RAS axis. Ang II produces skeletal muscle atrophy, a pathological condition characterised by the loss of strength and muscle mass. A feature of muscle atrophy is the decrease of the myofibrillar proteins produced by the activation of the ubiquitin-proteasome pathway (UPP), evidenced by the increase in the expression of two muscle-specific ubiquitin ligases: atrogin-1 and MuRF-1. In addition, it has been described that Ang II also induces myonuclear apoptosis during muscle atrophy. We assessed the effects of Ang (1-7) and Mas participation on myonuclear apoptosis during skeletal muscle atrophy induced by Ang II. Our results show that Ang (1-7), through Mas, prevents the effects induced by Ang II in the diaphragm muscles and decreases several events associated with apoptosis in the diaphragm (increased apoptotic nuclei, increased expression of caspase-8 and caspase-9, increased caspase-3 activity and increased Bax/Bcl-2 ratio). Concomitantly, Ang (1-7) also attenuates the decrease in fibre diameter and muscle strength, and prevents the increase in atrogin-1 and MuRF-1 during the muscle wasting induced by Ang II. Interestingly, these effects of Ang (1-7) are dependent on the Mas receptor. Thus, we demonstrated for the first time that Ang (1-7) prevents myonuclear apoptosis during the recovery of skeletal muscle atrophy induced by Ang II.

PMID:
25292283
DOI:
10.1007/s00424-014-1617-9
[Indexed for MEDLINE]

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