title: Ambient hypoxia enhances the loss of muscle mass after extensive injury.
abstract: Hypoxia induces a loss of skeletal muscle mass and alters myogenesis in vitro, but whether it affects muscle regeneration in vivo following injury remains to be elucidated. We hypothesized that hypoxia would impair the recovery of muscle mass during 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) conditions. Hypoxia impaired the formation and growth of new myofibers and enhanced the loss of muscle mass during the first 7 days of regeneration, but did not affect the final recovery of muscle mass at 28 days. The impaired regeneration under hypoxic conditions was associated with a blunted activation of mechanical target of rapamycin (mTOR) signaling as assessed by p70(S6K) and 4E-BP1 phosphorylation that was independent of Akt activation. The decrease in mTOR activity with hypoxia was consistent with the increase in AMP-activated protein kinase activity, but not related to the change in regulated in development and DNA response 1 protein content. Hypoxia increased the mRNA levels of the atrogene muscle ring finger-1 after 7 days of regeneration, though muscle atrophy F box transcript levels remained unchanged. The increase in MyoD and myogenin mRNA expression with regeneration was attenuated at 7 days with hypoxia. In conclusion, our results support the notion that the enhanced loss of muscle mass observed after 1 week of regeneration under hypoxic conditions could mainly result from the impaired formation and growth of new fibers resulting from a reduction in protein synthesis and satellite cell activity.
authors: Département Environnements opérationnels, Institut de Recherche Biomédicale des Armées, antenne de La Tronche, BP87, 38702, La Tronche, France, th.chaillou@gmail.com.
authors: T
authors: T
authors: Chaillou
authors: N
authors: N
authors: Koulmann
authors: A
authors: A
authors: Meunier
authors: P
authors: P
authors: Pugnière
authors: J J
authors: JJ
authors: McCarthy
authors: M
authors: M
authors: Beaudry
authors: X
authors: X
authors: Bigard
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D015687:Cell Hypoxia; D004546:Elapid Venoms / Q000633:toxicity; D005260:Female; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C000632146:Ddit4 protein, rat; C499526:Eif4ebp1 protein, rat; D004546:Elapid Venoms; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D017570:MyoD Protein; D010750:Phosphoproteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; C005082:notexin; C499086:Trim63 protein, rat; D044767:Ubiquitin-Protein Ligases; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases
references: Toxicon. 2003 Dec 15;42(8):915-31
references: 15019491
references: FASEB J. 2009 Oct;23(10):3335-46
references: 19528256
references: J Biophys Biochem Cytol. 1961 Feb;9:493-5
references: 13768451
references: Mol Cell. 2006 Feb 17;21(4):521-31
references: 16483933
references: Cell Prolif. 2010 Feb;43(1):1-8
references: 20070732
references: J Biol Chem. 2004 Apr 16;279(16):16332-8
references: 14754880
references: J Appl Physiol (1985). 2000 Feb;88(2):479-86
references: 10658014
references: Nature. 1994 Oct 27;371(6500):762-7
references: 7935836
references: Int J Biochem Cell Biol. 2005 Oct;37(10):1985-96
references: 16125108
references: J Am Geriatr Soc. 2011 Oct;59(10):1855-63
references: 22091499
references: Genes Dev. 2008 Jan 15;22(2):239-51
references: 18198340
references: Eur J Appl Physiol. 2008 Sep;104(1):57-65
references: 18535836
references: Mol Cell Biol. 2012 Jan;32(1):36-49
references: 22006022
references: Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
references: 12184808
references: PLoS One. 2012;7(6):e39124
references: 22720047
references: Cell. 2004 Oct 15;119(2):285-98
references: 15479644
references: J Appl Physiol (1985). 1988 Dec;65(6):2545-51
references: 3215854
references: Clin Exp Pharmacol Physiol. 1998 Feb;25(2):155-8
references: 9493507
references: Curr Biol. 2002 Aug 20;12(16):1419-23
references: 12194824
references: Mol Cell Biol. 2005 Apr;25(8):3040-55
references: 15798192
references: Curr Opin Clin Nutr Metab Care. 2011 Nov;14(6):548-53
references: 21934612
references: Mol Cell. 2008 Apr 25;30(2):214-26
references: 18439900
references: J Muscle Res Cell Motil. 2003;24(7):421-9
references: 14677645
references: Adv Exp Med Biol. 2000;475:111-21
references: 10849653
references: Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5857-62
references: 20231451
references: Mol Cell. 2004 May 7;14(3):395-403
references: 15125842
references: Physiol Rev. 2004 Jan;84(1):209-38
references: 14715915
references: Exp Physiol. 2010 Jun;95(6):723-35
references: 20176680
references: Am J Physiol Cell Physiol. 2009 Dec;297(6):C1434-44
references: 19794149
references: Circulation. 1992 Apr;85(4):1364-73
references: 1555280
references: Physiology (Bethesda). 2008 Jun;23:160-70
references: 18556469
references: Int J Biochem Cell Biol. 2005 Oct;37(10):1974-84
references: 16087388
references: Physiol Genomics. 2011 Feb 24;43(4):228-35
references: 21156833
references: Muscle Nerve. 2010 Nov;42(5):778-87
references: 20976781
references: Mol Cell Endocrinol. 2011 Jan 30;332(1-2):38-47
references: 20884321
references: Science. 2001 Nov 23;294(5547):1704-8
references: 11679633
references: J Appl Physiol (1985). 2007 Feb;102(2):573-81
references: 17038487
references: Br J Pharmacol. 1974 Sep;52(1):152P
references: 4451803
references: Nat Rev Mol Cell Biol. 2007 Oct;8(10):774-85
references: 17712357
references: Am J Physiol Regul Integr Comp Physiol. 2010 Jun;298(6):R1659-66
references: 20237300
references: Toxicon. 2003 Dec 15;42(8):933-45
references: 15019492
references: Am J Physiol Regul Integr Comp Physiol. 2012 Mar 1;302(5):R643-54
references: 22189670