Cobalt chloride, a chemical hypoxia-mimicking agent, suppresses myoblast differentiation by downregulating myogenin expression

Akira Wagatsuma, Masayuki Arakawa, Hanano Matsumoto, Ryoichi Matsuda, Takayuki Hoshino, Kunihiko Mabuchi

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Cobalt chloride can create hypoxia-like state in vitro (referred to as chemical hypoxia). Several studies have suggested that chemical hypoxia may cause deleterious effects on myogenesis. The intrinsic underlying mechanisms of myoblast differentiation, however, are not fully understood. Here, we show that cobalt chloride strongly suppresses myoblast differentiation in a dose-dependent manner. The impaired myoblast differentiation is accompanied by downregulation of myogenic regulatory factor myogenin. Under chemical hypoxia, myogenin stability is decreased at mRNA and protein levels. A muscle-specific E3 ubiquitin ligase MAFbx, which can target myogenin protein for proteasomal degradation, is upregulated along with changes in Akt/Foxo and AMPK/Foxo signaling pathways. A proteasome inhibitor completely prevents cobalt chloride-mediated decrease in myogenin protein. These results suggest that cobalt chloride might modulate myogenin expression at post-transcriptional and post-translational levels, resulting in the failure of the myoblasts to differentiate into myotubes.

Original languageEnglish
Pages (from-to)199-214
Number of pages16
JournalMolecular and Cellular Biochemistry
Volume470
Issue number1-2
DOIs
Publication statusPublished - 1 Jul 2020

Keywords

  • Chemical hypoxia
  • Cobalt chloride
  • MAFbx
  • Myogenin

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