title: Effect of acute environmental hypoxia on protein metabolism in human skeletal muscle.
abstract: Hypoxia-induced muscle wasting has been observed in several environmental and pathological conditions. However, the molecular mechanisms behind this loss of muscle mass are far from being completely elucidated, certainly in vivo. When studying the regulation of muscle mass by environmental hypoxia, many confounding factors have to be taken into account, such as decreased protein ingestion, sleep deprivation or reduced physical activity, which make difficult to know whether hypoxia per se causes a reduction in muscle mass.
  
  
  OBJECTIVE
  We hypothesized that acute exposure to normobaric hypoxia (11% O2 ) would repress the activation of the mTOR pathway usually observed after a meal and would activate the proteolytic pathways in skeletal muscle.
  
  
  METHODS
  Fifteen subjects were exposed passively for 4 h to normoxic and hypoxic conditions in a random order after consumption of a light breakfast. A muscle biopsy and a blood sample were taken before, after 1 and 4 h of exposure.
  
  
  RESULTS
  After 4 h, plasma insulin concentration and the phosphorylation state of PKB and S6K1 in skeletal muscle were higher in hypoxia than in normoxia (P < 0.05). At the same time, Redd1 mRNA level was upregulated (P < 0.05), whilst MAFbx mRNA decreased (P < 0.05) in hypoxia compared with normoxia. Proteasome, cathepsin L and calpain activities were not altered by environmental hypoxia.
  
  
  CONCLUSIONS
  Contrary to our hypothesis and despite an increase in the mRNA level of Redd1, an inhibitor of the mTORC1 pathway, short-term acute environmental hypoxia induced a higher response of PKB and S6K1 to a meal, which may be due to increased plasma insulin concentration.
authors: Department of Kinesiology, Exercise Physiology Research Group, FaBeR, KU Leuven, Leuven, Belgium.
authors: G
authors: G
authors: D'Hulst
authors: C
authors: C
authors: Jamart
authors: R
authors: R
authors: Van Thienen
authors: P
authors: P
authors: Hespel
authors: M
authors: M
authors: Francaux
authors: L
authors: L
authors: Deldicque
mesh_terms: D000208:Acute Disease; D001273:Atmosphere Exposure Chambers; D001786:Blood Glucose / Q000378:metabolism; D062408:Breakfast; D002154:Calpain / Q000378:metabolism; D056668:Cathepsin L / Q000378:metabolism; D018592:Cross-Over Studies; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D010092:Oximetry; D010100:Oxygen / Q000008:administration & dosage*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D001786:Blood Glucose; C469991:DDIT4 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007328:Insulin; D009124:Muscle Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C440907:FBXO32 protein, human; D044843:SKP Cullin F-Box Protein Ligases; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D002154:Calpain; C534281:CTSL protein, human; D056668:Cathepsin L; D046988:Proteasome Endopeptidase Complex; D010100:Oxygen; D006854:Hydrocortisone