Cited by 48Muscle Physiology and DisordersMuscle metabolism and nutritionNutrition and Health in Aging

l ‐glutamine Improves Skeletal Muscle Cell Differentiation and Prevents Myotube Atrophy After Cytokine (TNF‐α) Stress Via Reduced p38 MAPK Signal Transduction

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Girven, Matthew, Dugdale, Hannah F., Owens, Daniel J., Hughes, David C., Stewart, Claire E., Sharples, Adam P.·2016·Journal of Cellular Physiology

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. J. Cell. Physiol. 9999: 231: 2720-2732, 2016. © 2016 Wiley Periodicals, Inc.

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  • l-glutamine improves C2C12 cell differentiation and prevents TNF-α-induced myotube atrophy via reducing p38 MAPK signal transduction.

    “l-glutamine improves C2C12 cells differentiation and prevents TNF-α-induced myotube atrophy via reducing p38 mitogen-activated protein kinase (MAPK) signal transduction [35].”

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Research works printed but not linked: 2

  1. Labow BI, Souba WW. 2000. Glutamine. World J Surg 24(12):1503-1513.
  2. Meadows KA, Holly JM, Stewart CE. 2000. Tumor necrosis factor-alpha-induced apoptosis is associated with suppression of insulin-like growth factor binding protein-5 secretion in differentiating murine skeletal myoblasts. J Cell Physiol 183(3):330-337.

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Authors
Girven, M., Dugdale, H. F., Owens, D. J., Hughes, D. C., Stewart, C. E., & Sharples, A. P.
Affiliations
  • Liverpool John Moores University (GB)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
Sharples, Adam P.
Venue
Journal of Cellular Physiology
Publisher
Wiley
Published
2016-04-14
Volume
231
Issue
12
Pages
2720-2732
ISSN
  • 0021-9541 (ISSN-L)
  • 1097-4652
OpenAlex
W2299371824
Cited by
48
References
84
Citations by year
2026: 3 · 2025: 4 · 2024: 2 · 2023: 6 · 2022: 6 · 2021: 4 · 2020: 3 · 2019: 9 · 2018: 5 · 2017: 4 · 2016: 2
FWCI
3.46
Type
journal article
Language
en
Locations
  • Journal of Cellular Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • Liverpool John Moores University (submittedVersion)
Funders
Liverpool John Moores University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Keywords
glutamine, skeletal muscle atrophy, myotube atrophy, TNF-α, p38 MAPK signaling, myogenesis, C2C12 myoblasts, muscle atrophy, inflammation, FOXO3, myogenin, insulin-like growth factor I, glutamine synthetase, muscle catabolism
MeSH terms
Animals, Atrophy, Cell Differentiation, Cell Fusion, Cell Survival, Gene Expression Regulation, Glutamine, Phosphorylation, Stress, Physiological, Tumor Necrosis Factor-alpha, Muscle Fibers, Skeletal, MAP Kinase Signaling System, Muscle Development, Myoblasts, Skeletal, p38 Mitogen-Activated Protein Kinases, Cell Shape, Mice

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