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Published on: June 13, 2017
TNF-alpha inhibits adult fast myosin accumulation in myotubes
Vincent T Los1, Henk P Haagsman
1Division of Public Health and Food Safety, Faculty of Veterinary Medicine, Graduate School Animal Health, Utrecht University, P.O. Box 80175, 3508 TD Utrecht, The Netherlands.
Abstract:
Increased muscle catabolism is frequently observed in association with inflammatory disease. TNF-alpha has been implicated as an important messenger for muscle catabolism. Experiments with cultured muscle cells exposed to TNF-alpha have produced conflicting results. In a mouse cell line (C2C12), effects ranged from catabolic to anabolic. The results reported here offer an explanation for the observed discrepancies. It was found that TNF-alpha induced proliferation of myoblasts in fully differentiated cultures in low serum media and inhibited adult fast myosin accumulation under all conditions that were tested. Furthermore, TNF-alpha caused a proliferation dependent increase in total cell protein. Addition of insulin masked the effect of TNF-alpha on total protein, but not that on adult fast myosin accumulation. Discrepancies between studies can be explained by differences in proliferation rate, the dynamic nature of C2C12 myotube cultures and accumulation of adult fast myosin. The results are consistent with a dual role of TNF-alpha: stimulation of regeneration by short-term exposure and induction of muscle wasting by prolonged exposure.
Insights
Tumor necrosis factor-alpha (TNF-alpha) has a dual role in muscle cells. It can stimulate regeneration with short exposure but cause muscle wasting with prolonged exposure, explaining previous research discrepancies.
Area of Science:
- Muscle biology
- Cellular signaling
- Inflammatory disease research
Background:
- Muscle catabolism is linked to inflammatory diseases.
- Tumor necrosis factor-alpha (TNF-alpha) is a suspected mediator of muscle catabolism.
- Previous studies on TNF-alpha's effects on muscle cells yielded conflicting results.
Purpose of the Study:
- To investigate the discrepancies in previous research regarding TNF-alpha's effects on muscle cells.
- To elucidate the mechanisms behind TNF-alpha's influence on myoblast proliferation and protein synthesis.
Main Methods:
- Utilized the C2C12 mouse cell line for experiments.
- Exposed differentiated muscle cultures to TNF-alpha under varying serum conditions.
- Assessed myoblast proliferation, adult fast myosin accumulation, and total cell protein.
Main Results:
- TNF-alpha induced myoblast proliferation in differentiated cultures with low serum.
- TNF-alpha inhibited adult fast myosin accumulation universally.
- A proliferation-dependent increase in total cell protein was observed with TNF-alpha exposure.
- Insulin partially masked TNF-alpha's effect on total protein but not myosin accumulation.
Conclusions:
- Observed discrepancies in prior studies are attributable to variations in proliferation rates and myosin accumulation dynamics.
- TNF-alpha exhibits a dual role: promoting regeneration via short-term exposure and inducing muscle wasting via prolonged exposure.
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