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

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 104/3/625    most recent 00915.2007v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in 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 Web of Science (14) Citing Articles via Google Scholar Google Scholar Articles by Thomson, D. M. Articles by Gordon, S. E. Search for Related Content PubMed PubMed Citation Articles by Thomson, D. M. Articles by Gordon, S. E.

AMPK activation attenuates S6K1, 4E-BP1, and eEF2 signaling responses to high-frequency electrically stimulated skeletal muscle contractions

Human Performance Laboratory, Department of Exercise and Sport Science, and Department of Physiology, East Carolina University, Greenville, North Carolina

Submitted 24 August 2007 ; accepted in final form 2 January 2008

Regulation of protein translation through Akt and the downstream mammalian target of rapamycin (mTOR) pathway is an important component of the cellular response to hypertrophic stimuli. It has been proposed that 5'-AMP-activated protein kinase (AMPK) activation during muscle contraction may limit the hypertrophic response to resistance-type exercise by inhibiting translational signaling. However, experimental manipulation of AMPK activity during such a stimulus has not been attempted. Therefore, we investigated whether AMPK activation can attenuate the downstream signaling response of the Akt/mTOR pathway to electrically stimulated lengthening muscle contractions. Extensor digitorum longus muscles (n = 8/group) were subjected to a 22-min bout of lengthening contractions by high-frequency sciatic nerve electrical stimulation (STIM) in young adult (8 mo) Fischer 344 x Brown Norway male rats. Forty minutes before electrical stimulation, rats were subcutaneously injected with saline or 5-aminoimidazole-4-carboxamide-1–4-ribofuranoside (AICAR; 1 mg/g body wt), an AMPK activator. Stimulated and contralateral resting muscles were removed at 0, 20, and 40 min post-STIM, and AMPK, acetyl CoA carboxylase (ACC), Akt, eukaryotic initiation factor 4E-binding protein (4E-BP1), 70-kDa ribosomal protein S6 kinase (S6K1), and eukaryotic elongation factor 2 (eEF2) phosphorylations were assessed by Western blot. AICAR treatment increased (P 0.05) post-STIM AMPK (Thr¹⁷²) and ACC phosphorylation (Ser^79/221), inhibited post-STIM S6K1 (Thr³⁸⁹) and 4E-BP1 (gel shift) phosphorylation, and elevated post-STIM eEF2 phosphorylation (Thr⁵⁶). These findings suggest that translational signaling downstream of Akt/mTOR can be inhibited after lengthening contractions when preceded by AMPK activation and that energetic stress may be antagonistic to the hypertrophic translational signaling response to loaded muscle contractions.

high-frequency electrical stimulation; resistance exercise; AMP-activated protein kinase; mammalian target of rapamycin; protein synthesis

This article has been cited by other articles:

				L. Holm, G. van Hall, A. J. Rose, B. F. Miller, S. Doessing, E. A. Richter, and M. Kjaer Contraction intensity and feeding affect collagen and myofibrillar protein synthesis rates differently in human skeletal muscle Am J Physiol Endocrinol Metab, February 1, 2010; 298(2): E257 - E269. [Abstract] [Full Text] [PDF]

				T. K. O'Neil, L. R. Duffy, J. W. Frey, and T. A. Hornberger The role of phosphoinositide 3-kinase and phosphatidic acid in the regulation of mammalian target of rapamycin following eccentric contractions J. Physiol., July 15, 2009; 587(14): 3691 - 3701. [Abstract] [Full Text] [PDF]

				A. J. Rose and E. A. Richter Regulatory mechanisms of skeletal muscle protein turnover during exercise J Appl Physiol, May 1, 2009; 106(5): 1702 - 1711. [Abstract] [Full Text] [PDF]

				M. Miyazaki and K. A. Esser Cellular mechanisms regulating protein synthesis and skeletal muscle hypertrophy in animals J Appl Physiol, April 1, 2009; 106(4): 1367 - 1373. [Abstract] [Full Text] [PDF]

				A. J. Rose, B. Bisiani, B. Vistisen, B. Kiens, and E. A. Richter Skeletal muscle eEF2 and 4EBP1 phosphorylation during endurance exercise is dependent on intensity and muscle fiber type Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2009; 296(2): R326 - R333. [Abstract] [Full Text] [PDF]

				R. Zamilpa and M. L. Lindsey AMP Activated Protein Kinase 2 Protection During Hypertension-Induced Hypertrophy: A Common Mediator in the Signaling Crossroads Hypertension, November 1, 2008; 52(5): 813 - 815. [Full Text] [PDF]

				C. Cao, S. Lu, R. Kivlin, B. Wallin, E. Card, A. Bagdasarian, T. Tamakloe, W.-m. Chu, K.-l. Guan, and Y. Wan AMP-activated Protein Kinase Contributes to UV- and H2O2-induced Apoptosis in Human Skin Keratinocytes J. Biol. Chem., October 24, 2008; 283(43): 28897 - 28908. [Abstract] [Full Text] [PDF]

				A. M. Pruznak, A. A. Kazi, R. A. Frost, T. C. Vary, and C. H. Lang Activation of AMP-Activated Protein Kinase by 5-Aminoimidazole-4-Carboxamide-1-{beta}-D-Ribonucleoside Prevents Leucine-Stimulated Protein Synthesis in Rat Skeletal Muscle J. Nutr., October 1, 2008; 138(10): 1887 - 1894. [Abstract] [Full Text] [PDF]

				S. B. Wilkinson, S. M. Phillips, P. J. Atherton, R. Patel, K. E. Yarasheski, M. A. Tarnopolsky, and M. J. Rennie Differential effects of resistance and endurance exercise in the fed state on signalling molecule phosphorylation and protein synthesis in human muscle J. Physiol., August 1, 2008; 586(15): 3701 - 3717. [Abstract] [Full Text] [PDF]