Akt/mTOR pathway contributes to skeletal muscle anti-atrophic effect of aerobic exercise training in heart failure mice

Author(s):Show less -

Bacurau, Aline V. N. ^[1] ; Jannig, Paulo R. ^[1] ; de Moraes, Wilson M. A. M. ^[2] ; Cunha, Telma F. ^[1] ; Medeiros, Alessandra ^[2] ; Barberi, Laura ^[3] ; Coelho, Marcele A. ^[1] ; Bacurau, Reury F. P. ^[4] ; Ugrinowitsch, Carlos ^[1] ; Musaro, Antonio ^{[3, 5]} ; Brum, Patricia C. ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Biosci, Santos - Brazil

^[3] Univ Roma La Sapienza, Unit Histol & Med Embryol, DAHFMO, Inst Pasteur Cenci Bolognetti, Piazzale Aldo Moro 5, I-00185 Rome - Italy

^[4] Univ Sao Paulo, Sch Arts, Human, Sci, BR-05508 Sao Paulo - Brazil

^[5] Ist Italiano Tecnol, Ctr Life Nano Sci Sapienza, Rome - Italy

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF CARDIOLOGY; v. 214, p. 137-147, JUL 1 2016.
• Web of Science Citations: 9

Abstract

Background: Exercise intolerance is one of the main clinical symptoms of heart failure (HF) and is associated with skeletal muscle wasting due to an imbalance between proteolysis and protein synthesis. In this study, we tested whether aerobic exercise training (AET) would counteract skeletal muscle atrophy by activating IGF-I/Akt/mTOR pathway in HF mice. Methods: Sympathetic hyperactivity induced HF mice were assigned into 8-week moderate intensity AET. Untrained wild type and HF mice were used as control. Soleus cross sectional area was evaluated by histochemistry and motor performance by rotarod. 26S proteasome activity was assessed by fluorimetric assay, and components of IGF-I/Akt/mTOR pathway or myostatin pathway by qRT-PCR or immunoblotting. A different subset of mice was used to evaluate the relative contribution of mTOR inhibition (rapamycin) or activation (leucine) on AET-induced changes in muscle mass regulation. Results: AET prevented exercise intolerance and impaired motor performance in HF mice. These effects were associated with attenuation of soleus atrophy. Rapamycin treatment precluded AET effects on soleus mass in HF mice suggesting the involvement of IGF signaling pathway in this response. In fact, AET increased IGF-I Ea and IGF-I Pan mRNA levels, while it reduced myostatin and Smad2 mRNA levels in HF mice. At protein levels, AET prevented reduced expression levels of IGF-I, pAkt (at basal state), as well as, p4E-BP1 and pP70(S6K) (leucine-stimulated state) in HF mice. Additionally, AET prevented 26S proteasome hyperactivity in HF mice. Conclusions: Taken together, our data provide evidence for AET-induced activation of IGF-I/Akt/mTOR signaling pathway counteracting HF-induced muscle wasting. (C) 2016 Elsevier Ireland Ltd. All rights reserved. (AU)

• FAPESP's process: 14/25957-9 - Influence of aerobic fitness in redox homeostasis: identification and biological implications of cysteine residues oxidation in cardiac and skeletal muscle proteins
• Grantee: Rodrigo Wagner Alves de Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/22817-6 - Effects of concurrent training with vascular occlusion on muscle hypertrophy in elderly
• Grantee: Carlos Ugrinowitsch
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/50048-1 - Cellular and functional bases of exercise in cardiovascular diseases
• Grantee: Carlos Eduardo Negrão
• Support Opportunities: Research Projects - Thematic Grants