Immediate response of mammalian target of rapamycin (mTOR)-mediated signalling following acute resistance exercise in rat skeletal muscle

• Published in: The Journal of physiology Vol. 553; no. 1; pp. 213 - 220
• Main Authors: Bolster, Douglas R., Kubica, Neil, Crozier, Stephen J., Williamson, David L., Farrell, Peter A., Kimball, Scot R., Jefferson, Leonard S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK The Physiological Society 15-11-2003; Blackwell Publishing Ltd; Blackwell Science Inc
• Subjects: Animals; Eukaryotic Initiation Factors - metabolism; Male; Muscle Proteins - physiology; Muscle, Skeletal - physiology; Original; Ornithine Decarboxylase - metabolism; Phosphorylation; Physical Exertion - physiology; Protein Kinases - physiology; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Ribosomal Protein S6 - metabolism; Signal Transduction - physiology; Sirolimus - pharmacology; TOR Serine-Threonine Kinases; Up-Regulation - drug effects; Up-Regulation - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2003.047019

The purpose of the present investigation was to determine whether mammalian target of rapamycin (mTOR)-mediated signalling
and some key regulatory proteins of translation initiation are altered in skeletal muscle during the immediate phase of recovery
following acute resistance exercise. Rats were operantly conditioned to reach an illuminated bar located high on a Plexiglass
cage, such that the animals completed concentric and eccentric contractions involving the hindlimb musculature. Gastrocnemius
muscle was extracted immediately after acute exercise and 5, 10, 15, 30 and 60 min of recovery. Phosphorylation of protein
kinase B (PKB) on Ser-473 peaked at 10 min of recovery (282 % of control, P < 0.05) with no significant changes noted for mTOR phosphorylation on Ser-2448. Eukaryotic initiation factor (eIF) 4E-binding
protein-1 (4E-BP1) and S6 kinase-1 (S6K1), both downstream effectors of mTOR, were altered during recovery as well. 4E-BP1
phosphorylation was significantly elevated at 10 min (292 %, P < 0.01) of recovery. S6K1 phosphorylation on Thr-389 demonstrated a trend for peak activation at 10 min following exercise
(336 %, P = 0.06) with ribosomal protein S6 phosphorylation being maximally activated at 15 min of recovery (647 %, P < 0.05). Components of the eIF4F complex were enhanced during recovery as eIF4E association with eIF4G peaked at 10 min (292
%, P < 0.05). Events regulating the binding of initiator methionyl-tRNA to the 40S ribosomal subunit were assessed through eIF2B
activity and eIF2α phosphorylation on Ser-51. No differences were noted with either eIF2B or eIF2α. Collectively, these results
provide strong evidence that mTOR-mediating signalling is transiently upregulated during the immediate period following resistance
exercise and this response may constitute the most proximal growth response of the cell.