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Increasing autophagy does not affect neurogenic muscle atrophy

Eva Pigna, Krizia Sanna, Dario Coletti, Zhenlin Li, Ara Parlakian, Sergio Adamo, Viviana Moresi
  • Eva Pigna http://orcid.org/0000-0003-1755-8978
    Department of Anatomy, Histology, Forensic Medicine & Orthopedics, Histology & Medical Embryology Section, Sapienza University of Rome, Italy
  • Krizia Sanna http://orcid.org/0000-0003-0476-7332
    Department of Anatomy, Histology, Forensic Medicine & Orthopedics, Histology & Medical Embryology Section, Sapienza University of Rome,, Italy
  • Dario Coletti http://orcid.org/0000-0001-7373-1953
    Department of Anatomy, Histology, Forensic Medicine & Orthopedics, Histology & Medical Embryology Section, Sapienza University of Rome, Italy; Interuniversity Institute of Myology, Italy; Sorbonne Université, CNRS UMR 8256-INSERM ERL U1164, IBPS B2A Department of Biological Adaptation and Aging, Paris, France

Abstract

Physiological autophagy plays a crucial role in the regulation of muscle mass and metabolism, while the excessive induction or the inhibition of the autophagic flux contributes to the progression of several diseases. Autophagy can be activated by different stimuli, including cancer, exercise, caloric restriction and denervation. The latter leads to muscle atrophy through the activation of catabolic pathways, i.e. the ubiquitin-proteasome system and autophagy. However, the kinetics of autophagy activation and the upstream molecular pathways in denervated skeletal muscle have not been reported yet. In this study, we characterized the kinetics of autophagic induction, quickly triggered by denervation, and report the Akt/mTOR axis activation. Besides, with the aim to assess the relative contribution of autophagy in neurogenic muscle atrophy, we triggered autophagy with different stimuli along with denervation, and observed that four week-long autophagic induction, by either intermitted fasting or rapamycin treatment, did not significantly affect muscle mass loss. We conclude that: i) autophagy does not play a major role in inducing muscle loss following denervation; ii) nonetheless, autophagy may have a regulatory role in denervation induced muscle atrophy, since it is significantly upregulated as early as eight hours after denervation; iii) Akt/mTOR axis, AMPK and FoxO3a are activated consistently with the progression of muscle atrophy, further highlighting the complexity of the signaling response to the atrophying stimulus deriving from denervation.

Keywords

Denervation; Autophagy; Neurogenic muscle atrophy; Intermittent fasting; Rapamycin

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Submitted: 2018-07-11 18:20:45
Published: 2018-08-23 17:36:05
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Copyright (c) 2018 Eva Pigna, Krizia Sanna, Dario Coletti, Zhenlin Li, Ara Parlakian, Sergio Adamo, Viviana Moresi

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