Ambient hypoxia enhances the loss of muscle mass after extensive injury

Chaillou, Thomas; Koulmann, Nathalie; A, Meunier; Pugnière, P.; McCarthy, John J.; Beaudry, Michèle; Bigard, Xavier

doi:10.1007/s00424-013-1336-7

Cited by 38 publications

(50 citation statements)

References 41 publications

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“…Some works reported an increase in MAFbx mRNA [74,119], while this expression in not always observed after prolonged exposure [101,123]. The other well studied E3 ligase MuRF1 presents a similar expression pattern with an increase during the first week of hypoxia exposure [74,123] and a return to basal level during longer exposure [101,123]. These patterns of MuRF1 and MAFbx expression in response to hypoxia are similar to those reported during unloading and muscle inactivity [129].…”

Section: Hypoxia-related Regulation Of Proteolytic Systemssupporting

confidence: 66%

“…Kinetics is likely of particular importance when studying these markers. Some works reported an increase in MAFbx mRNA [74,119], while this expression in not always observed after prolonged exposure [101,123]. The other well studied E3 ligase MuRF1 presents a similar expression pattern with an increase during the first week of hypoxia exposure [74,123] and a return to basal level during longer exposure [101,123].…”

Section: Hypoxia-related Regulation Of Proteolytic Systemsmentioning

confidence: 61%

“…c, d representative pictures from hematoxylin-eosin stained cross sections of rat plantaris muscle c in normoxia or d after 12 days at 5500 m (obtained from [118] with permission). Data for muscle weight and FCSA were obtained from [19, 101,118,123,146,149,[151][152][153][154][155] and [55,91,96,101,142,151,153,155], respectively HIF-1-driven skeletal muscle adaptations to chronic hypoxia: Molecular insights into muscle… that use ATP (triglyceride and protein synthesis). In subjects exposed to 11.5 % O 2 for 20 min, Wadley et al did not reported any alteration of skeletal muscle AMPKa1 activity, AMPKa2 activity, AMPKa Thr172 phosphorylation, or ACCb Ser221 phosphorylation (a direct target of AMPK) [122].…”

Section: Regulation Of Muscle Mass Structural Modificationsmentioning

confidence: 99%

“…In subjects exposed to 11.5 % O 2 for 20 min, Wadley et al did not reported any alteration of skeletal muscle AMPKa1 activity, AMPKa2 activity, AMPKa Thr172 phosphorylation, or ACCb Ser221 phosphorylation (a direct target of AMPK) [122]. While AMPK can be transiently activated by acute hypoxia, this activation does not seem to persist after several days at altitude [73,101,118,123]. These observations are consistent with the stability of AMP, ADP and ATP concentrations after 21 days at 4300 m [55] and do not support a role for AMPK in Akt/mTOR inhibition during skeletal muscle hypoxia in vivo.…”

Section: Regulation Of Muscle Mass Structural Modificationsmentioning

confidence: 99%

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HIF-1-driven skeletal muscle adaptations to chronic hypoxia: molecular insights into muscle physiology

Favier

Britto

Freyssenet

et al. 2015

Cell. Mol. Life Sci.

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Skeletal muscle is a metabolically active tissue and the major body protein reservoir. Drop in ambient oxygen pressure likely results in a decrease in muscle cells oxygenation, reactive oxygen species (ROS) overproduction and stabilization of the oxygen-sensitive hypoxia-inducible factor (HIF)-1α. However, skeletal muscle seems to be quite resistant to hypoxia compared to other organs, probably because it is accustomed to hypoxic episodes during physical exercise. Few studies have observed HIF-1α accumulation in skeletal muscle during ambient hypoxia probably because of its transient stabilization. Nevertheless, skeletal muscle presents adaptations to hypoxia that fit with HIF-1 activation, although the exact contribution of HIF-2, I kappa B kinase and activating transcription factors, all potentially activated by hypoxia, needs to be determined. Metabolic alterations result in the inhibition of fatty acid oxidation, while activation of anaerobic glycolysis is less evident. Hypoxia causes mitochondrial remodeling and enhanced mitophagy that ultimately lead to a decrease in ROS production, and this acclimatization in turn contributes to HIF-1α destabilization. Likewise, hypoxia has structural consequences with muscle fiber atrophy due to mTOR-dependent inhibition of protein synthesis and transient activation of proteolysis. The decrease in muscle fiber area improves oxygen diffusion into muscle cells, while inhibition of protein synthesis, an ATP-consuming process, and reduction in muscle mass decreases energy demand. Amino acids released from muscle cells may also have protective and metabolic effects. Collectively, these results demonstrate that skeletal muscle copes with the energetic challenge imposed by O2 rarefaction via metabolic optimization.

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Section: Hypoxia-related Regulation Of Proteolytic Systemssupporting

confidence: 66%

Section: Hypoxia-related Regulation Of Proteolytic Systemsmentioning

confidence: 61%

Section: Regulation Of Muscle Mass Structural Modificationsmentioning

confidence: 99%

Section: Regulation Of Muscle Mass Structural Modificationsmentioning

confidence: 99%

See 2 more Smart Citations

HIF-1-driven skeletal muscle adaptations to chronic hypoxia: molecular insights into muscle physiology

Favier

Britto

Freyssenet

et al. 2015

Cell. Mol. Life Sci.

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“…In rodents, the phosphorylation state of the mTORC1 pathway in basal conditions is either unchanged9,48,49 or reduced21 after exposure to hypoxia for ∼2–3 weeks. The present study is the first to measure the phosphorylation state of different components of the mTORC1 pathway in humans exposed to environmental hypoxia for >2 weeks.…”

Section: Discussionmentioning

confidence: 99%

Fifteen days of 3,200 m simulated hypoxia marginally regulates markers for protein synthesis and degradation in human skeletal muscle

D’Hulst¹,

Ferri²,

Naslain³

et al. 2016

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Chronic hypoxia leads to muscle atrophy. The molecular mechanisms responsible for this phenomenon are not well defined in vivo. We sought to determine how chronic hypoxia regulates molecular markers of protein synthesis and degradation in human skeletal muscle and whether these regulations were related to the regulation of the hypoxia-inducible factor (HIF) pathway. Eight young male subjects lived in a normobaric hypoxic hotel (FiO2 14.1%, 3,200 m) for 15 days in well-controlled conditions for nutrition and physical activity. Skeletal muscle biopsies were obtained in the musculus vastus lateralis before (PRE) and immediately after (POST) hypoxic exposure. Intramuscular hypoxia-inducible factor-1 alpha (HIF-1α) protein expression decreased (−49%, P=0.03), whereas hypoxia-inducible factor-2 alpha (HIF-2α) remained unaffected from PRE to POST hypoxic exposure. Also, downstream HIF-1α target genes VEGF-A (−66%, P=0.006) and BNIP3 (−24%, P=0.002) were downregulated, and a tendency was measured for neural precursor cell expressed, developmentally Nedd4 (−47%, P=0.07), suggesting lowered HIF-1α transcriptional activity after 15 days of exposure to environmental hypoxia. No difference was found on microtubule-associated protein 1 light chain 3 type II/I (LC3b-II/I) ratio, and P62 protein expression tended to increase (+45%, P=0.07) compared to PRE exposure levels, suggesting that autophagy was not modulated after chronic hypoxia. The mammalian target of rapamycin complex 1 pathway was not altered as Akt, mammalian target of rapamycin, S6 kinase 1, and 4E-binding protein 1 phosphorylation did not change between PRE and POST. Finally, myofiber cross-sectional area was unchanged between PRE and POST. In summary, our data indicate that moderate chronic hypoxia differentially regulates HIF-1α and HIF-2α, marginally affects markers of protein degradation, and does not modify markers of protein synthesis or myofiber cross-sectional area in human skeletal muscle.

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Hypoxia Impairs Muscle Function and Reduces Myotube Size in Tissue Engineered Skeletal Muscle

et al. 2017

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Contemporary tissue engineered skeletal muscle models display a high degree of physiological accuracy compared with native tissue, and therefore may be excellent platforms to understand how various pathologies affect skeletal muscle. Chronic obstructive pulmonary disease (COPD) is a lung disease which causes tissue hypoxia and is characterized by muscle fiber atrophy and impaired muscle function. In the present study we exposed engineered skeletal muscle to varying levels of oxygen (O2; 21–1%) for 24 h in order to see if a COPD like muscle phenotype could be recreated in vitro, and if so, at what degree of hypoxia this occurred. Maximal contractile force was attenuated in hypoxia compared to 21% O2; with culture at 5% and 1% O2 causing the most pronounced effects with 62% and 56% decrements in force, respectively. Furthermore at these levels of O2, myotubes within the engineered muscles displayed significant atrophy which was not seen at higher O2 levels. At the molecular level we observed increases in mRNA expression of MuRF‐1 only at 1% O2 whereas MAFbx expression was elevated at 10%, 5%, and 1% O2. In addition, p70S6 kinase phosphorylation (a downstream effector of mTORC1) was reduced when engineered muscle was cultured at 1% O2, with no significant changes seen above this O2 level. Overall, these data suggest that engineered muscle exposed to O2 levels of ≤5% adapts in a manner similar to that seen in COPD patients, and thus may provide a novel model for further understanding muscle wasting associated with tissue hypoxia. J. Cell. Biochem. 118: 2599–2605, 2017. © 2017 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.

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Ambient hypoxia enhances the loss of muscle mass after extensive injury

Cited by 38 publications

References 41 publications

HIF-1-driven skeletal muscle adaptations to chronic hypoxia: molecular insights into muscle physiology

HIF-1-driven skeletal muscle adaptations to chronic hypoxia: molecular insights into muscle physiology

Fifteen days of 3,200 m simulated hypoxia marginally regulates markers for protein synthesis and degradation in human skeletal muscle

Hypoxia Impairs Muscle Function and Reduces Myotube Size in Tissue Engineered Skeletal Muscle

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