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L-glutamine improves skeletal muscle cell differentiation and prevents myotube atrophy after cytokine (TNF-α) stress via reduced p38 MAPK signal transduction

Girven, M and Dugdale, HF and Owens, DJ and Hughes, DC and Stewart, CE and Sharples, AP (2016) L-glutamine improves skeletal muscle cell differentiation and prevents myotube atrophy after cytokine (TNF-α) stress via reduced p38 MAPK signal transduction. Journal of Cellular Physiology. ISSN 1097-4652

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Abstract

Tumour Necrosis Factor- Alpha (TNF-α) is chronically elevated in conditions where skeletal muscle loss occurs. As L-glutamine can dampen the effects of inflamed environments, we investigated the role of L-glutamine in both differentiating C2C12 myoblasts and existing myotubes in the absence/presence of TNF-α (20 ng.ml−1) ± L-glutamine (20 mM).TNF-α reduced the proportion of cells in G1 phase, as well as biochemical (CK activity) and morphological differentiation (myotube number), with corresponding reductions in transcript expression of: Myogenin, Igf-I and Igfbp5. Furthermore, when administered to mature myotubes, TNF-α induced myotube loss and atrophy underpinned by reductions in Myogenin, Igf-I, Igfbp2 and glutamine synthetase and parallel increases in Fox03, Cfos, p53 and Bid gene expression. Investigation of signaling activity suggested that Akt and ERK1/2 were unchanged, JNK increased (non-significantly) whereas P38 MAPK substantially and significantly increased in both myoblasts and myotubes in the presence of TNF-α. Importantly, 20 mM L-glutamine reduced p38 MAPK activity in TNF-α conditions back to control levels, with a corresponding rescue of myoblast differentiation and a reversal of atrophy in myotubes. L-glutamine resulted in upregulation of genes associated with growth and survival including; Myogenin, Igf-Ir, Myhc2 & 7, Tnfsfr1b, Adra1d and restored atrophic gene expression of Fox03 back to baseline in TNF-α conditions. In conclusion, L-glutamine supplementation rescued suppressed muscle cell differentiation and prevented myotube atrophy in an inflamed environment via regulation of p38 MAPK. L-glutamine administration could represent an important therapeutic strategy for reducing muscle loss in catabolic diseases and inflamed ageing. This article is protected by copyright. All rights reserved

Item Type: Article
Additional Information: This is the accepted version of the following article: "L-glutamine improves skeletal muscle cell differentiation and prevents myotube atrophy after cytokine (TNF-α) stress via reduced p38 MAPK signal transduction", which has been published in final form at http://dx.doi.org/10.1002/jcp.25380
Uncontrolled Keywords: 1116 Medical Physiology
Subjects: R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions: Sport & Exercise Sciences
Publisher: Wiley
Related URLs:
Date Deposited: 21 Mar 2016 12:36
Last Modified: 17 Mar 2017 00:50
DOI or Identification number: 10.1002/jcp.25380
URI: http://researchonline.ljmu.ac.uk/id/eprint/3305

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