Effect of Hypoxia on the Muscle Fiber Switching Signal Pathways CnA/NFATc1 and Myostatin in Mouse Myocytes

Acta Histochem. 2019 Jul;121(5):539-545. doi: 10.1016/j.acthis.2019.04.001. Epub 2019 Apr 30.

Abstract

This study investigated the effects of a CoCl2-simulated hypoxic environment on the muscle fiber switching signaling pathways calcineurin A/nuclear factor of activated T cells cytoplasmic 1 (CnA/NFATc1) and myostatin. In this study, C2C12 muscle cells were cultured in vitro under CoCl2-simulated chemical hypoxic conditions, the expression levels of CnA and myostatin were detected through qRT-PCR and Western blot analyses, and a positioning study of NFATc1 was carried out by immunofluorescence labeling. Results showed that CoCl2 treatment significantly increased the expression levels of CnA and myostatin. Moreover, the position of NFATc1 expression changed; actually, its expression in the nucleus considerably increased. Furthermore, CoCl2-induced hypoxia inhibited the differentiation of C2C12 cells and reduced the expression levels of many slow- and fast-twitch muscles marker genes, but immunofluorescence staining results showed that the proportion of MyHC I type muscle fiber increased after CoCl2 treatment. The hypoxic environment simulated by CoCl2 can activate the signaling pathways CnA/NFATc1 and myostatin and increases the proportion of MyHC I type muscle fibers.

Keywords: C2C12; CnA/NFATc1; CoCl; Myostatin.

MeSH terms

  • Animals
  • Blotting, Western
  • Calcineurin / metabolism*
  • Cell Hypoxia / physiology
  • Cells, Cultured
  • Cobalt
  • Mice
  • Muscle, Skeletal / metabolism*
  • Myostatin / genetics
  • Myostatin / metabolism*
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction
  • Transcriptome

Substances

  • Mstn protein, mouse
  • Myostatin
  • NFATC Transcription Factors
  • Nfatc1 protein, mouse
  • Cobalt
  • Calcineurin
  • cobaltous chloride