PMID- 23974966 OWN - NLM STAT- MEDLINE DCOM- 20141011 LR - 20211203 IS - 1432-2013 (Electronic) IS - 0031-6768 (Print) IS - 0031-6768 (Linking) VI - 466 IP - 3 DP - 2014 Mar TI - Ambient hypoxia enhances the loss of muscle mass after extensive injury. PG - 587-98 LID - 10.1007/s00424-013-1336-7 [doi] AB - 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. FAU - Chaillou, T AU - Chaillou T AD - Departement Environnements operationnels, Institut de Recherche Biomedicale des Armees, antenne de La Tronche, BP87, 38702, La Tronche, France, th.chaillou@gmail.com. FAU - Koulmann, N AU - Koulmann N FAU - Meunier, A AU - Meunier A FAU - Pugniere, P AU - Pugniere P FAU - McCarthy, J J AU - McCarthy JJ FAU - Beaudry, M AU - Beaudry M FAU - Bigard, X AU - Bigard X LA - eng GR - R01 AR061939/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130824 PL - Germany TA - Pflugers Arch JT - Pflugers Archiv : European journal of physiology JID - 0154720 RN - 0 (Carrier Proteins) RN - 0 (Ddit4 protein, rat) RN - 0 (Eif4ebp1 protein, rat) RN - 0 (Elapid Venoms) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Muscle Proteins) RN - 0 (MyoD Protein) RN - 0 (Phosphoproteins) RN - 0 (RNA, Messenger) RN - 0 (Repressor Proteins) RN - 0 (Transcription Factors) RN - 0 (Tripartite Motif Proteins) RN - 37223-96-4 (notexin) RN - EC 2.3.2.27 (Trim63 protein, rat) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/metabolism MH - Animals MH - Carrier Proteins/metabolism MH - Cell Hypoxia MH - Elapid Venoms/toxicity MH - Female MH - Hypoxia/*metabolism/physiopathology MH - Intracellular Signaling Peptides and Proteins MH - Muscle Fibers, Skeletal/drug effects/*metabolism/pathology/physiology MH - Muscle Proteins/genetics/metabolism MH - MyoD Protein/genetics/metabolism MH - Phosphoproteins/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - RNA, Messenger/genetics/metabolism MH - Rats MH - Rats, Wistar MH - *Regeneration MH - Repressor Proteins/genetics/metabolism MH - Ribosomal Protein S6 Kinases/metabolism MH - Signal Transduction MH - TOR Serine-Threonine Kinases/metabolism MH - Transcription Factors MH - Tripartite Motif Proteins MH - Ubiquitin-Protein Ligases/genetics/metabolism PMC - PMC4878136 MID - NIHMS785892 EDAT- 2013/08/27 06:00 MHDA- 2014/10/12 06:00 PMCR- 2016/05/24 CRDT- 2013/08/27 06:00 PHST- 2013/05/09 00:00 [received] PHST- 2013/08/10 00:00 [accepted] PHST- 2013/08/09 00:00 [revised] PHST- 2013/08/27 06:00 [entrez] PHST- 2013/08/27 06:00 [pubmed] PHST- 2014/10/12 06:00 [medline] PHST- 2016/05/24 00:00 [pmc-release] AID - 10.1007/s00424-013-1336-7 [doi] PST - ppublish SO - Pflugers Arch. 2014 Mar;466(3):587-98. doi: 10.1007/s00424-013-1336-7. Epub 2013 Aug 24.