Ibuprofen treatment blunts early translational signaling responses in human skeletal muscle following resistance exercise

J Appl Physiol (1985). 2014 Jul 1;117(1):20-8. doi: 10.1152/japplphysiol.01299.2013. Epub 2014 May 15.


Cyclooxygenase-1 and -2 pathway-derived prostaglandins (PGs) have been implicated in adaptive muscle responses to exercise, but the role of PGs in contraction-induced muscle signaling has not been determined. We investigated the effect of inhibition of cyclooxygenase-1 and -2 activities with the nonsteroidal anti-inflammatory drug ibuprofen on human muscle signaling responses to resistance exercise. Subjects orally ingested 1,200 mg ibuprofen (or placebo control) in three 400-mg doses administered ∼30 min before and ∼6 h and ∼12 h following a bout of unaccustomed resistance exercise (80% one repetition maximum). Muscle biopsies were obtained at rest (preexercise), immediately postexercise (0 h), 3 h postexercise, and at 24 h of recovery. In the placebo (PLA) group, phosphorylation of ERK1/2 (Thr202/Tyr204), ribosomal protein S6 kinase (RSK, Ser380), mitogen-activated kinase 1 (Mnk1, Thr197/202), and p70S6 kinase (p70S6K, Thr421/Ser424) increased at both 0 and 3 h postexercise, with delayed elevation of phospho (p)-p70S6K (Thr389) and p-rpS6 (Ser235/S36 and Ser240/244) at 3 h postexercise. Only p-ERK1/2 (Thr202/Tyr204) remained significantly elevated in the 24-h postexercise biopsy. Ibuprofen treatment prevented sustained elevation of MEK-ERK signaling at 3 h (p-ERK1/2, p-RSK, p-Mnk1, p-p70S6K Thr421/Ser424) and 24 h (p-ERK1/2) postexercise, and this was associated with suppressed phosphorylation of ribosomal protein S6 (Ser235/236 and Ser240/244). Early contraction-induced p-Akt (Ser473) and p-p70S6K (Thr389) were not influenced by ibuprofen, but p-p70S6K (Thr389) remained elevated 24 h postexercise only in those receiving ibuprofen treatment. Early muscle signaling responses to resistance exercise are, in part, ibuprofen sensitive, suggesting that PGs are important signaling molecules during early postexercise recovery.

Keywords: ERK; NSAID; inflammation; mTOR; prostaglandins; protein synthesis.

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Exercise / physiology*
  • Humans
  • Ibuprofen / therapeutic use*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Male
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiology
  • Peptide Chain Elongation, Translational / drug effects*
  • Peptide Chain Elongation, Translational / physiology
  • Phosphorylation / drug effects
  • Phosphorylation / physiology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Ribosomal Protein S6 / metabolism
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • Young Adult


  • Anti-Inflammatory Agents, Non-Steroidal
  • Ribosomal Protein S6
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Ibuprofen