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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
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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]
Número total de Autores: 11
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: INTERNATIONAL JOURNAL OF CARDIOLOGY; v. 214, p. 137-147, JUL 1 2016.
Citações Web of Science: 9
Resumo

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)

Processo FAPESP: 03/10442-9 - Caracterização fenotípica do músculo esquelético na cardiomiopatia induzida por hiperatividade simpática
Beneficiário:Aline Villa Nova Bacurau
Linha de fomento: Bolsas no Brasil - Mestrado
Processo FAPESP: 10/50048-1 - Bases celulares e funcionais do exercício físico na doença cardiovascular
Beneficiário:Carlos Eduardo Negrão
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 14/25957-9 - Influência da aptidão aeróbica na homeostase redox: identificação e implicação biológica da oxidação de resíduos cisteína em proteínas do músculo cardíaco e esquelético
Beneficiário:Rodrigo Wagner Alves de Souza
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 12/22817-6 - Efeito do treinamento concorrente com oclusão vascular na hipertrofia muscular de idosos
Beneficiário:Carlos Ugrinowitsch
Linha de fomento: Auxílio à Pesquisa - Regular