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

Mol Cell Biochem. 2014 May;390(1-2):31-40. doi: 10.1007/s11010-013-1952-8. Epub 2014 Jan 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Hypoxia / physiology*
  • Female
  • Membrane Proteins / metabolism
  • Mitochondrial Proteins / metabolism
  • Muscle Fibers, Slow-Twitch / metabolism
  • Muscle Fibers, Slow-Twitch / physiology*
  • Muscle, Skeletal / growth & development*
  • Muscle, Skeletal / metabolism
  • Myosin Heavy Chains / metabolism
  • Phenotype
  • Rats
  • Rats, Wistar
  • Regeneration*


  • BNIP3 protein, rat
  • Membrane Proteins
  • Mitochondrial Proteins
  • Myosin Heavy Chains