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Effect of hypoxia exposure on the recovery of skeletal muscle phenotype during regeneration

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Abstract

Hypoxia impairs the muscle fibre-type shift from fast-to-slow during post-natal development; however, this adaptation could be a consequence of the reduced voluntary physical activity associated with hypoxia exposure rather than the result of hypoxia per se. Moreover, muscle oxidative capacity could be reduced in hypoxia, particularly when hypoxia is combined with additional stress. Here, we used a model of muscle regeneration to mimic the fast-to-slow fibre-type conversion observed during post-natal development. We hypothesised that hypoxia would impair the recovery of the myosin heavy chain (MHC) profile and oxidative capacity during muscle regeneration. To test this hypothesis, the soleus muscle of female rats was injured by notexin and allowed to recover for 3, 7, 14 and 28 days under normoxia or hypobaric hypoxia (5,500 m altitude) conditions. Ambient hypoxia did not impair the recovery of the slow MHC profile during muscle regeneration. However, hypoxia moderately decreased the oxidative capacity (assessed from the activity of citrate synthase) of intact muscle and delayed its recovery in regenerated muscle. Hypoxia transiently increased in both regenerated and intact muscles the content of phosphorylated AMPK and Pgc-1α mRNA, two regulators involved in mitochondrial biogenesis, while it transiently increased in intact muscle the mRNA level of the mitophagic factor BNIP3. In conclusion, hypoxia does not act to impair the fast-to-slow MHC isoform transition during regeneration. Hypoxia alters the oxidative capacity of intact muscle and delays its recovery in regenerated muscle; however, this adaptation to hypoxia was independent of the studied regulators of mitochondrial turn-over.

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Acknowledgments

We thank Dr. Nadine Simler (Institut de Recherche Biomédicale des Armées) for helpful technical assistance, Dr. André Peinnequin and Dr. Pascal Pugnière (Institut de Recherche Biomédicale des Armées) for useful discussions about RT-qPCR analysis and Dr. John J. McCarthy (Department of Physiology, University of Kentucky, USA) for careful reading of the manuscript. This work was supported by a predoctoral fellowship from the Ministère de I’Enseignement Supérieur et de la Recherche to TC and by the Association Française contre les Myopathies (Grant number 13955 to MB and XB).

Conflict of interest

No conflicts of interest, financial or otherwise, are declared by the author.

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Authors and Affiliations

  1. Département Environnements opérationnels, Institut de Recherche Biomédicale des Armées, antenne de La Tronche, BP 87, 38702, La Tronche Cedex, France

    Thomas Chaillou, N. Koulmann, A. Meunier, R. Chapot, B. Serrurier & X. Bigard

  2. Ecole du Val-de-Grâce, 1 Place Alphonse Laveran, 75005, Paris, France

    N. Koulmann & X. Bigard

  3. Laboratoire « Réponses cellulaires et fonctionnelles à l’hypoxie », EA2363, Sorbonne-Paris-Cité, Université Paris 13, 93017, Bobigny Cedex, France

    M. Beaudry

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  1. Thomas Chaillou
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Correspondence to Thomas Chaillou.

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Chaillou, T., Koulmann, N., Meunier, A. et al. Effect of hypoxia exposure on the recovery of skeletal muscle phenotype during regeneration. Mol Cell Biochem 390, 31–40 (2014). https://doi.org/10.1007/s11010-013-1952-8

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