HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Williamson, D. L. Articles by Jefferson, L. S. Search for Related Content PubMed PubMed Citation Articles by Williamson, D. L. Articles by Jefferson, L. S.

Time course changes in signaling pathways and protein synthesis in C₂C₁₂ myotubes following AMPK activation by AICAR

Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania

Submitted 21 November 2005 ; accepted in final form 29 January 2006

The role of the AMP-activated kinase (AMPK) as a metabolic sensor in skeletal muscle has been far better characterized for glucose and fat metabolism than for protein metabolism. Therefore, the studies presented here were designed to examine the effects of 5-aminoimidazole-4-carboxamide-1--D-ribonucleoside (AICAR)-induced AMPK signaling on effector mechanisms of mRNA translation and protein synthesis in cultures of C₂C₁₂ myotubes. The findings show that, following AICAR (2 mM) treatment, AMPK phosphorylation was increased within 15 min and remained elevated throughout a 60-min time course. In association with the increase in AMPK phosphorylation, global rates of protein synthesis declined to 90, 70, and 63% of the control values at the 15-, 30-, and 60-min time points, respectively. By 60 min, polysomes disaggregated into free ribosomal subunits, suggesting an inhibition of initiation of mRNA translation. However, phosphorylation of eukaryotic elongation factor 2 was increased at 15 and 30 min but then declined to control values by 60 min, suggesting a transient inhibition of translation elongation. The decline in protein synthesis and changes in mRNA translation were associated with a repression of the mammalian target of rapamycin (mTOR) signaling pathway, as indicated by increased association of Hamartin with Tuberin, increased association of regulatory associated protein of mTOR with mTOR, and dephosphorylation of the downstream targets ribosomal protein S6 kinase-1 and eukaryotic initiation factor 4E-binding protein-1. They were also associated with activation of the MAPK signaling pathway, as indicated by increased phosphorylation of MEK1/2 and ERK1/2 and the downstream target eIF4E. Overall, the data support the conclusion that AICAR-induced AMPK activation suppresses protein synthesis through concurrent repression of mTOR signaling and activation of MAPK signaling, the combination of which modulates transient changes in the initiation and elongation phases of mRNA translation.

5-aminoimidazole-4-carboxamide-1--D-ribonucleoside; eukaryotic elongation factor 2; mammalian target of rapamycin; extracellular signal-regulated protein kinase; Tuberin; regulatory associated protein of mammalian target of rapamycin

This article has been cited by other articles:

				S. L. McGee, K. J. Mustard, D. G. Hardie, and K. Baar Normal hypertrophy accompanied by phosphoryation and activation of AMP-activated protein kinase {alpha}1 following overload in LKB1 knockout mice J. Physiol., March 15, 2008; 586(6): 1731 - 1741. [Abstract] [Full Text] [PDF]

				D. M. Thomson, C. A. Fick, and S. E. Gordon AMPK activation attenuates S6K1, 4E-BP1, and eEF2 signaling responses to high-frequency electrically stimulated skeletal muscle contractions J Appl Physiol, March 1, 2008; 104(3): 625 - 632. [Abstract] [Full Text] [PDF]

				A. Suryawan, R. A. Orellana, H. V. Nguyen, A. S. Jeyapalan, J. R. Fleming, and T. A. Davis Activation by insulin and amino acids of signaling components leading to translation initiation in skeletal muscle of neonatal pigs is developmentally regulated Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1597 - E1605. [Abstract] [Full Text] [PDF]

				A. S. Jeyapalan, R. A. Orellana, A. Suryawan, P. M. J. O'Connor, H. V. Nguyen, J. Escobar, J. W. Frank, and T. A. Davis Glucose stimulates protein synthesis in skeletal muscle of neonatal pigs through an AMPK- and mTOR-independent process Am J Physiol Endocrinol Metab, August 1, 2007; 293(2): E595 - E603. [Abstract] [Full Text] [PDF]

				S. Fujita, H. C. Dreyer, M. J. Drummond, E. L. Glynn, J. G. Cadenas, F. Yoshizawa, E. Volpi, and B. B. Rasmussen Nutrient signalling in the regulation of human muscle protein synthesis J. Physiol., July 15, 2007; 582(2): 813 - 823. [Abstract] [Full Text] [PDF]

				R. A. Frost and C. H. Lang Protein kinase B/Akt: a nexus of growth factor and cytokine signaling in determining muscle mass J Appl Physiol, July 1, 2007; 103(1): 378 - 387. [Abstract] [Full Text] [PDF]

				S. Glund, A. Deshmukh, Y. C. Long, T. Moller, H. A. Koistinen, K. Caidahl, J. R. Zierath, and A. Krook Interleukin-6 Directly Increases Glucose Metabolism in Resting Human Skeletal Muscle Diabetes, June 1, 2007; 56(6): 1630 - 1637. [Abstract] [Full Text] [PDF]