Martin_et_al-2017-Journal_of_Cellular_Biochemistry (2).pdf (655.49 kB)
Download file

Hypoxia impairs muscle function and reduces myotube size in tissue engineered skeletal muscle

Download (655.49 kB)
journal contribution
posted on 30.03.2017, 15:06 by Neil MartinNeil Martin, Kathryn Aguilar-Agon, G.P. Robinson, Darren Player, Mark Turner, S.D. Myers, Mark LewisMark Lewis
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 characterised by muscle fibre atrophy and impaired muscle function. In the present study we exposed engineered skeletal muscle to varying levels of oxygen (O2; 21-1%) for 24 hours in order to see if a COPD like muscle phenotype could be recreated in vitro, and if so, at what degree of hypoxia this occured. 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%, 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.

Funding

This article was funded by the RCUK under grant number EP/L015072/1.

History

School

  • Sport, Exercise and Health Sciences

Published in

Journal of Cellular Biochemistry

Volume

118

Issue

9

Pages

2599-2605

Citation

MARTIN, N.R.W. ... et al, 2017. Hypoxia impairs muscle function and reduces myotube size in tissue engineered skeletal muscle. Journal of Cellular Biochemistry, 118 (9), pp. 2599–2605.

Publisher

Wiley (© the authors)

Version

NA (Not Applicable or Unknown)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) licence. Full details of this licence are available at: http://creativecommons.org/licenses/ by/4.0/

Acceptance date

07/03/2017

Publication date

2017-03-10

Notes

This is an Open Access article published by Wiley and distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0). More details are available here: https://creativecommons.org/licenses/by/4.0/

ISSN

1097-4644

Language

en

Usage metrics

Keywords

Licence

Exports