Aline V N Bacurau1, Paulo R Jannig1, Wilson M A M de Moraes2, Telma F Cunha1, Alessandra Medeiros2, Laura Barberi3, Marcele A Coelho1, Reury F P Bacurau4, Carlos Ugrinowitsch1, Antonio Musarò5, Patricia C Brum6. 1. School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil. 2. Department of Biosciences, Federal University of São Paulo, Santos, Brazil. 3. Institute Pasteur-Cenci Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy. 4. School of Arts, Sciences, Humanities, University of São Paulo, SP, Brazil. 5. Institute Pasteur-Cenci Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy; Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Rome, Italy. 6. School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil. Electronic address: pcbrum@usp.br.
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.
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.
Authors: Aline R R Lima; Luana U Pagan; Ricardo L Damatto; Marcelo D M Cezar; Camila Bonomo; Mariana J Gomes; Paula F Martinez; Daniele M Guizoni; Dijon H S Campos; Felipe C Damatto; Katashi Okoshi; Marina P Okoshi Journal: Oncotarget Date: 2017-08-24
Authors: Daniele J Feriani; Hélio J Coelho-Júnior; Juliana C M F de Oliveira; Maria A Delbin; Cristiano T Mostarda; Paulo M M Dourado; Érico C Caperuto; Maria C C Irigoyen; Bruno Rodrigues Journal: Front Physiol Date: 2018-02-12 Impact factor: 4.566
Authors: Ligia M Antunes-Correa; Patricia F Trevizan; Aline V N Bacurau; Larissa Ferreira-Santos; João L P Gomes; Ursula Urias; Patricia A Oliveira; Maria Janieire N N Alves; Dirceu R de Almeida; Patricia C Brum; Edilamar M Oliveira; Ludhmila Hajjar; Roberto Kalil Filho; Carlos Eduardo Negrão Journal: J Cachexia Sarcopenia Muscle Date: 2019-11-19 Impact factor: 12.910