Pflügers Archiv - European Journal of Physiology

, Volume 455, Issue 6, pp 1129–1140

Effects of contraction and insulin on protein synthesis, AMP-activated protein kinase and phosphorylation state of translation factors in rat skeletal muscle

Authors

  • Lisa Miranda
    • Hormone and Metabolic Research Unit, de Duve InstituteUniversité catholique de Louvain
  • Sandrine Horman
    • Hormone and Metabolic Research Unit, de Duve InstituteUniversité catholique de Louvain
  • Isabelle De Potter
    • Hormone and Metabolic Research Unit, de Duve InstituteUniversité catholique de Louvain
  • Louis Hue
    • Hormone and Metabolic Research Unit, de Duve InstituteUniversité catholique de Louvain
  • Jørgen Jensen
    • National Institute of Occupational Health
    • Hormone and Metabolic Research Unit, de Duve InstituteUniversité catholique de Louvain
Signal Transduction

DOI: 10.1007/s00424-007-0368-2

Cite this article as:
Miranda, L., Horman, S., De Potter, I. et al. Pflugers Arch - Eur J Physiol (2008) 455: 1129. doi:10.1007/s00424-007-0368-2

Abstract

In rat epitrochlearis skeletal muscle, contraction inhibited the basal and insulin-stimulated rates of protein synthesis by 75 and 70%, respectively, while increasing adenosine monophosphate-activated protein kinase (AMPK) activity. Insulin, on the other hand, stimulated protein synthesis (by 30%) and increased p70 ribosomal protein S6 kinase (p70S6K) Thr389, 40S ribosomal protein S6 (rpS6) Ser235/236, rpS6 Ser240/244 and eukaryotic initiation factor-4E-binding protein-1 (4E-BP1) Thr37/46 phosphorylation over basal values. Electrical stimulation had no effect on mammalian target of rapamycin complex 1 (mTORC1) signalling, as reflected by the lack of reduction in basal levels of p70S6K, rpS6 Ser235/236, rpS6 Ser240/244 and 4E-BP1 phosphorylation, but did antagonize mTORC1 signalling after stimulation of the pathway by insulin. Eukaryotic elongation factor-2 (eEF2) Thr56 phosphorylation increased rapidly on electrical stimulation reaching a maximum at 1 min, whereas AMPK Thr172 phosphorylation slowly increased to reach threefold after 30 min. Eukaryotic elongation factor-2 kinase (eEF2K) was not activated after 30 min of contraction when AMPK was activated. This could not be explained by the expression of a tissue-specific isoform of eEF2K in skeletal muscle lacking the Ser398 AMPK phosphorylation site. Therefore, in this skeletal muscle system, the contraction-induced inhibition of protein synthesis could not be attributed to a reduction in mTORC1 signalling but could be due to an increase in eEF2 phosphorylation independent of AMPK activation.

Keywords

PKBeEF2KeEF2mTORC1p70S6K4E-BP1rpS6PRAS40

Abbreviations

4E-BP1

eukaryotic initiation factor-4E-binding protein-1

ACC

acetyl-CoA carboxylase

AICAR

5-aminoimidazole-4-carboxamide riboside

AMPK

AMP-activated protein kinase

eEF2

eukaryotic elongation factor-2

eEF2K

eukaryotic elongation factor-2 kinase

mTOR

mammalian target of rapamycin

mTORC1

mammalian target of rapamycin complex 1

PRAS40

proline-rich Akt/PKB substrate 40 kDa

p70S6K

p70 ribosomal protein S6 kinase

rp S6

40S ribosomal protein S6

Copyright information

© Springer-Verlag 2007