IGF-I does not prevent myotube atrophy caused by proinflammatory cytokines despite activation of Akt/Foxo and GSK-3beta pathways and inhibition of atrogin-1 mRNA.

Dehoux, Mischaël;Gobier, Catherine;Lause, Pascale;Bertrand, Luc;Thissen, Jean-Paul;et.al.
(2007) American journal of physiology. Endocrinology and metabolism — Vol. 292, n° 1, p. E145-150 (2007)

Files

ManuscritMischael2007.pdf
  • Restricted Access
  • Adobe PDF
  • 236.62 KB
Request a copy

Details

Authors
  • Dehoux, MischaëlUCLouvain
    Author
  • Gobier, CatherineUCLouvain
    Author
  • Lause, PascaleUCLouvain
    Author
  • Bertrand, LucUCLouvain
    Author
  • Ketelslegers, Jean-MarieUCLouvain
    Author
  • Thissen, Jean-Paulorcid-logoUCLouvain
    Author
Show more
Abstract
Myofibrillar protein loss occurring in catabolic situations is considered to be mediated by the release of proinflammatory cytokines and associated with a decrease in circulating and muscle levels of insulin-like growth factor I (IGF-I). In this paper, we investigated whether the C(2)C(12) myotube atrophy caused in vitro by TNF-alpha/IFN-gamma cytokines might be reversed by exogenous IGF-I. Our results showed that, despite the presence of TNF-alpha/IFN-gamma, IGF-I retained its full ability to induce the phosphorylation of Akt, Foxo3a, and GSK-3beta (respectively, 16-fold, 9-fold, and 2-fold) together with a decrease in atrogin-1 mRNA (-39%, P < 0.001). Although this ubiquitin ligase has been reported to accelerate the degradation of MyoD, a myogenic transcription factor driving the transcription of myosin heavy chain (MHC), IGF-I failed to blunt the reduction of MyoD and MHC caused by TNF-alpha/IFN-gamma. Moreover, IGF-I only very slightly attenuated the myotube atrophy induced by TNF-alpha/IFN-gamma (TNF-alpha/IFN-gamma 15.48 mum alone vs. TNF-alpha/IFN-gamma/IGF-I 16.97 mum, P < 0.001). In conclusion, our data show that IGF-I does not reverse the myotube atrophy induced by TNF-alpha/IFN-gamma despite the phosphorylation of Foxo and GSK-3beta and the downregulation of atrogin-1 mRNA. Our study suggests therefore that factors other than IGF-I decrease are responsible for the muscle atrophy caused by proinflammatory cytokines.
Affiliations

Citations

  • APA
  • Chicago
  • FWB

Dehoux, M., Gobier, C., Lause, P., Bertrand, L., Ketelslegers, J.-M., & Thissen, J.-P. (2007). IGF-I does not prevent myotube atrophy caused by proinflammatory cytokines despite activation of Akt/Foxo and GSK-3beta pathways and inhibition of atrogin-1 mRNA. American journal of physiology. Endocrinology and metabolism, 292(1), E145-150. https://doi.org/10.1152/ajpendo.00085.2006 (Original work published 2007)