Myostatin inhibits eEF2K-eEF2 by regulating AMPK to suppress protein synthesis

Biochem Biophys Res Commun. 2017 Dec 9;494(1-2):278-284. doi: 10.1016/j.bbrc.2017.10.040. Epub 2017 Oct 9.

Abstract

Growth of skeletal muscle is dependent on the protein synthesis, and the rate of protein synthesis is mainly regulated in the stage of translation initiation and elongation. Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily, is a negative regulator of protein synthesis. C2C12 myotubes was incubated with 0, 0.01, 0.1, 1, 2, 3 μg/mL myostatin recombinant protein, and then we detected the rates of protein synthesis by the method of SUnSET. We found that high concentrations of myostatin (2 and 3 μg/mL) inhibited protein synthesis by blocking mTOR and eEF2K-eEF2 pathway, while low concentration of myostatin (0.01, 0.1 and 1 μg/mL) regulated eEF2K-eEF2 pathway activity to block protein synthesis without affected mTOR pathway, and myostatin inhibited eEF2K-eEF2 pathway through regulating AMPK pathway to suppress protein synthesis. It provided a new mechanism for myostatin regulating protein synthesis and treating muscle atrophy.

Keywords: AMPK; Myostatin; Protein synthesis; eEF2K-eEF2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / genetics*
  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Cell Line, Transformed
  • Dose-Response Relationship, Drug
  • Elongation Factor 2 Kinase / antagonists & inhibitors*
  • Elongation Factor 2 Kinase / genetics
  • Elongation Factor 2 Kinase / metabolism
  • Gene Expression Regulation
  • Mice
  • Muscle Development / genetics
  • Myoblasts / cytology
  • Myoblasts / drug effects*
  • Myoblasts / metabolism
  • Myostatin / genetics
  • Myostatin / metabolism
  • Myostatin / pharmacology*
  • Peptide Elongation Factor 2 / antagonists & inhibitors*
  • Peptide Elongation Factor 2 / genetics
  • Peptide Elongation Factor 2 / metabolism
  • Protein Biosynthesis / drug effects*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Mstn protein, mouse
  • Myostatin
  • Peptide Elongation Factor 2
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • Eef2k protein, mouse
  • Elongation Factor 2 Kinase
  • AMP-Activated Protein Kinases