Activation of ERK by sodium tungstate induces protein synthesis and prevents protein degradation in rat L6 myotubes

FEBS Lett. 2014 Jun 27;588(14):2246-54. doi: 10.1016/j.febslet.2014.05.004. Epub 2014 May 17.

Abstract

The balance between the rates of protein synthesis and degradation in muscle is regulated by PI3K/Akt signaling. Here we addressed the effect of ERK activation by sodium tungstate on protein turnover in rat L6 myotubes. Phosphorylation of ERK by this compound increased protein synthesis by activating MTOR and prevented dexamethasone-induced protein degradation by blocking FoxO3a activity, but it did not alter Akt phosphorylation. Thus, activation of ERK by tungstate improves protein turnover in dexamethasone-treated cells. On the basis of our results, we propose that tungstate be considered an alternative to IGF-I and its analogs in the prevention of skeletal muscle atrophy.

Keywords: Extracellular signal-regulated kinases 1 and 2; Forkhead box O Family of Transcription Factors; LC3; Mechanistic target of rapamycin; Skeletal muscle; Sodium tungstate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dexamethasone / pharmacology
  • Drug Evaluation, Preclinical
  • Enzyme Activation
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors / metabolism
  • Glucocorticoids / pharmacology
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • MAP Kinase Signaling System*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism*
  • Muscular Atrophy / prevention & control
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Biosynthesis / drug effects*
  • Proteolysis / drug effects*
  • Rats
  • Sequestosome-1 Protein
  • TOR Serine-Threonine Kinases / metabolism
  • Transcription, Genetic / drug effects
  • Tungsten Compounds / pharmacology*
  • Ubiquitin / genetics
  • Ubiquitin / metabolism

Substances

  • FOXO3 protein, rat
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors
  • Glucocorticoids
  • Heat-Shock Proteins
  • LC3 protein, rat
  • Microtubule-Associated Proteins
  • Sequestosome-1 Protein
  • Sqstm1 protein, rat
  • Tungsten Compounds
  • Ubiquitin
  • sodium tungstate(VI)
  • Dexamethasone
  • TOR Serine-Threonine Kinases
  • mTOR protein, rat
  • Extracellular Signal-Regulated MAP Kinases
  • Proteasome Endopeptidase Complex