L-glutamine Improves Skeletal Muscle Cell Differentiation and Prevents Myotube Atrophy After Cytokine (TNF-alpha) Stress Via Reduced p38 MAPK Signal Transduction

Abstract

Tumour Necrosis Factor-Alpha (TNF-a) 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-a (20?ng?·?ml-1)?±?l-glutamine (20?mM). TNF-a 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-a 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-a. Importantly, 20?mM l-glutamine reduced p38 MAPK activity in TNF-a 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-a 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.

Citation

(2016). L-glutamine Improves Skeletal Muscle Cell Differentiation and Prevents Myotube Atrophy After Cytokine (TNF-alpha) Stress Via Reduced p38 MAPK Signal Transduction. Journal of Cellular Physiology, 2720 - 2732. https://doi.org/10.1002/jcp.25380

• Acceptance Date: Mar 17, 2016
• Publication Date: Apr 14, 2016
• Journal: JOURNAL OF CELLULAR PHYSIOLOGY
• Print ISSN: 0021-9541
• Publisher: Wiley
• Pages: 2720 - 2732
• DOI: https://doi.org/10.1002/jcp.25380
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1002/jcp.25380/abstract