| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Attenuates Insulin-Stimulated Protein Synthesis In Cultures Of C2C12 Myotubes Through a MEK1-sensitive Mechanism
1 Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA, USA
* To whom correspondence should be addressed. E-mail: skimball{at}psu.edu.
Insulin and TNF-
exert opposing effects upon skeletal muscle protein synthesis that are
mediated in part by the rapamycin sensitive, mammalian Target of Rapamycin (mTOR) pathway
and the PD-98059-sensitive, extracellular signal-regulated kinase (ERK) 1/2 pathway. The present study examined the separate and combined effects of insulin (INS), TNF, PD-98059, or dnMEK1 adenovirus on the translational control of protein synthesis in C2C12 myotubes. Cultures were treated with INS, TNF, PD-98059, dnMEK1 or a combination of INS+TNF with PD-98059 or dnMEK1. INS stimulated protein synthesis, enhanced eIF4E.eIF4G association and eIF4G phosphorylation, and repressed eIF4E.4E-BP1 association versus control. INS also promoted phosphorylation of ERK1/2, S6K1, and 4E-BP1, and dephosphorylation of eIF4E.
TNF alone did not have an effect on protein synthesis (vs. control), eIF4E.eIF4G association, or
the phosphorylation of eIF4G, S6K1, or 4E-BP1, although it transiently increased ERK1/2 and eIF4E phosphorylation. When the myotubes were treated with a combination of TNF and INS, the cytokine blocked the insulin-induced stimulation of protein synthesis. This appeared to be
due to an attenuation of insulin-stimulated eIF4E.eIF4G association, because other stimulatory effects of INS, e.g. phosphorylation of ERK1/2, 4E-BP1, S6K1, eIF4G, and eIF4E and
eIF4E.4E-BP1 association, were unaffected. Lastly, treatment of myotubes with PD-98059 or
dnMEK1 adenovirus prior to TNF+INS addition resulted in a derepression of protein synthesis and the association of eIF4G with eIF4E. These findings suggest that TNF abrogates insulininduced stimulation of protein synthesis in myotubes through a decrease in eIF4F complex
assembly, independent of S6K1 and 4E-BP1 signaling and dependent on a MEK1-sensitive signaling pathway.
This article has been cited by other articles:
|
|
 |
|
  C. P. Lambert, N. R. Wright, B. N. Finck, and D. T. Villareal Exercise but not diet-induced weight loss decreases skeletal muscle inflammatory gene expression in frail obese elderly persons J Appl Physiol, August 1, 2008; 105(2): 473 - 478. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Plaisance, C. Morandi, C. Murigande, and M. Brink TNF-{alpha} increases protein content in C2C12 and primary myotubes by enhancing protein translation via the TNF-R1, PI3K, and MEK Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E241 - E250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Louis, U. Raue, Y. Yang, B. Jemiolo, and S. Trappe Time course of proteolytic, cytokine, and myostatin gene expression after acute exercise in human skeletal muscle J Appl Physiol, November 1, 2007; 103(5): 1744 - 1751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Lang, R. A. Frost, and T. C. Vary Regulation of muscle protein synthesis during sepsis and inflammation Am J Physiol Endocrinol Metab, August 1, 2007; 293(2): E453 - E459. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Flynn, B. K. McFarlin, and M. M. Markofski State of the Art Reviews: The Anti-Inflammatory Actions of Exercise Training American Journal of Lifestyle Medicine, May 1, 2007; 1(3): 220 - 235. [Abstract] [PDF]
|
|
|
|
|
|
J. M. Peterson, K. D. Feeback, J. H. Baas, and F. X. Pizza Tumor necrosis factor-{alpha} promotes the accumulation of neutrophils and macrophages in skeletal muscle J Appl Physiol, November 1, 2006; 101(5): 1394 - 1399. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
