The impact of intracellular aminopeptidase on C2C12 myoblast proliferation and differentiation

Biochem Biophys Res Commun. 2020 Apr 9;524(3):608-613. doi: 10.1016/j.bbrc.2020.01.115. Epub 2020 Feb 3.


The ubiquitin-proteasome pathway is essential for skeletal muscle growth and development. Proteasomes generate oligopeptides in the cytoplasm, and these peptides are considered to be rapidly degraded to amino acids by several intracellular aminopeptidases. However, the role of intracellular aminopeptidases in muscle growth remains unknown. In this study, therefore, we investigated the role of intracellular aminopeptidases in C2C12 myoblast proliferation and differentiation. Inhibition of intracellular aminopeptidases by Bestatin methyl ester (Bes-ME) decreased leucine and alanine aminopeptidase activity, and impaired proliferation and differentiation of C2C12 myoblasts. Furthermore, we observed that the inhibition of intracellular aminopeptidases reduced intracellular levels of amino acid and ATP level, and suppressed the phosphorylation of the mTOR pathway. These results suggested that intracellular aminopeptidases affect C2C12 myoblast proliferation and differentiation via mTOR pathway; however, further studies are required to clarify the role of aminopeptidase in skeletal muscle.

Keywords: Aminopeptidase; C2C12; Proteasome; Skeletal muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amino Acids / metabolism
  • Aminopeptidases / antagonists & inhibitors
  • Aminopeptidases / metabolism*
  • Animals
  • Cell Differentiation* / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Intracellular Space / enzymology*
  • Mice
  • Myoblasts / cytology*
  • Myoblasts / drug effects
  • Myoblasts / enzymology*
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism


  • Amino Acids
  • Enzyme Inhibitors
  • Adenosine Triphosphate
  • TOR Serine-Threonine Kinases
  • Aminopeptidases