title: Effect of hypoxia exposure on the phenotypic adaptation in remodelling skeletal muscle submitted to functional overload.
abstract: OBJECTIVE
  To determine whether hypoxia influences the phenotypic adaptation of skeletal muscle induced by mechanical overload.
  
  
  METHODS
  Plantaris muscles of female rats were submitted to mechanical overload following synergist ablation. After 3 days of overload, rats were exposed to either hypobaric hypoxia (equivalent to 5500 m) or normoxia. Muscles were collected after 5, 12 and 56 days of overload (i.e. after 3, 9 and 53 days of hypoxia). We determined the myosin heavy chain (MHC) distribution, mRNA levels of myocyte-enriched calcineurin-integrating protein 1 (MCIP1) to indirectly assess calcineurin activity, the changes in oxidative capacity from the activities of citrate synthase (CS) and cytochrome c oxidase (COX), and the expression of regulators involved in mitochondrial biogenesis (Pgc-1α, NRF1 and Tfam) and degradation (BNIP-3).
  
  
  RESULTS
  Hypoxia did not alter the fast-to-slow MHC shift and the increase in calcineurin activity induced by overload; it only transiently slowed down the overload-induced transition in MHC isoforms. Hypoxia similarly decreased CS and COX activities in overloaded and control muscles. Nuclear respiratory factor 1 (NRF1) and transcription factor A (Tfam) mRNA and BNIP-3 protein were not influenced by hypoxia in overloaded muscles, whereas Pgc-1α mRNA and protein contents did not correlate with changes in oxidative capacity.
  
  
  CONCLUSIONS
  Hypoxia is not a critical stimulus to modulate the fast-to-slow MHC transition associated with overload. Thus, the impairment of the fast-to-slow fibre shift often observed during post-natal development in hypoxia could be explained by the lower voluntary locomotor activity associated with hypoxia. Hypoxia alters mitochondrial oxidative capacity, but this adaptive response is similar in overloaded and control muscles.
authors.affiliation: Département Environnements opérationnels, Institut de Recherche Biomédicale des Armées, antenne de La Tronche, La Tronche, France.
authors.forename: T
authors.initials: T
authors.lastname: Chaillou
authors.forename: N
authors.initials: N
authors.lastname: Koulmann
authors.forename: A
authors.initials: A
authors.lastname: Meunier
authors.forename: A
authors.initials: A
authors.lastname: Malgoyre
authors.forename: B
authors.initials: B
authors.lastname: Serrurier
authors.forename: M
authors.initials: M
authors.lastname: Beaudry
authors.forename: X
authors.initials: X
authors.lastname: Bigard
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical; D014157:Transcription Factors / Q000378:metabolism; D016474:Weight-Bearing / Q000502:physiology*
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; D019703:Calcineurin; D018995:Myosin Heavy Chains
keywords: Pgc-1α; altitude; calcineurin; mitochondria; myosin heavy chain isoforms