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Autophagy signaling in skeletal muscle of infarcted rats

Jannig, Paulo R.; Moreira, Jose Bianco Nascimento; Bechara, Luiz R.G.; Bozi, Luiz H.M.; Bacurau, Aline V.; Monteiro, Alex W.A.; Dourado, Paulo M.; Wisløff, Ulrik; Brum, Patricia Chakur
Journal article, Peer reviewed
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URI
http://hdl.handle.net/11250/2367289
Date
2014
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  • Institutt for sirkulasjon og bildediagnostikk [1383]
  • Publikasjoner fra CRIStin - NTNU [26648]
Original version
PLoS ONE 2014, 9(1)   10.1371/journal.pone.0085820
Abstract
Background:

Heart failure (HF)-induced skeletal muscle atrophy is often associated to exercise intolerance and poor prognosis. Better understanding of the molecular mechanisms underlying HF-induced muscle atrophy may contribute to the development of pharmacological strategies to prevent or treat such condition. It has been shown that autophagy-lysosome system is an important mechanism for maintenance of muscle mass. However, its role in HF-induced myopathy has not been addressed yet. Therefore, the aim of the present study was to evaluate autophagy signaling in myocardial infarction (MI)-induced muscle atrophy in rats.

Methods/Principal Findings:

Wistar rats underwent MI or Sham surgeries, and after 12 weeks were submitted to echocardiography, exercise tolerance and histology evaluations. Cathepsin L activity and expression of autophagy-related genes and proteins were assessed in soleus and plantaris muscles by fluorimetric assay, qRT-PCR and immunoblotting, respectively. MI rats displayed exercise intolerance, left ventricular dysfunction and dilation, thereby suggesting the presence of HF. The key findings of the present study were: a) upregulation of autophagy-related genes (GABARAPL1, ATG7, BNIP3, CTSL1 and LAMP2) was observed only in plantaris while muscle atrophy was observed in both soleus and plantaris muscles, and b) Cathepsin L activity, Bnip3 and Fis1 protein levels, and levels of lipid hydroperoxides were increased specifically in plantaris muscle of MI rats.

Conclusions:

Altogether our results provide evidence for autophagy signaling regulation in HF-induced plantaris atrophy but not soleus atrophy. Therefore, autophagy-lysosome system is differentially regulated in atrophic muscles comprising different fiber-types and metabolic characteristics.
Publisher
Public Library of Science
Journal
PLoS ONE

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