Iron accumulation causes impaired myogenesis correlated with MAPK signaling pathway inhibition by oxidative stress

Yasumasa Ikeda, Akiho Satoh, Yuya Horinouchi, Hirofumi Hamano, Hiroaki Watanabe, Mizuki Imao, Masaki Imanishi, Yoshito Zamami, Kenshi Takechi, Yuki Izawa-Ishizawa, Licht Miyamoto, Tasuku Hirayama, Hideko Nagasawa, Keisuke Ishizawa, Ken Ichi Aihara, Koichiro Tsuchiya, Toshiaki Tamaki

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Skeletal muscle atrophy is caused by disruption in the homeostatic balance of muscle degeneration and regeneration under various pathophysiological conditions. We have previously reported that iron accumulation induces skeletal muscle atrophy via a ubiquitin ligase–dependent pathway. However, the potential effect of iron accumulation on muscle regeneration remains unclear. To examine the effect of iron accumulation on myogenesis, we used a mouse model with cardiotoxin (CTX)-induced muscle regeneration in vivo and C2C12 mouse myoblast cells in vitro. In mice with iron overload, the skeletal muscles exhibited increased oxidative stress and decreased expression of satellite cell markers. Following CTX-induced muscle injury, these mice also displayed delayed muscle regeneration with a decrease in the size of regenerating myofibers, reduced expression of myoblast differentiation markers, and decreased phosphorylation of MAPK signaling pathways. In vitro, iron overload also suppressed the differentiation of C2C12 myoblast cells but the suppression could be reversed by superoxide scavenging using tempol. Excess iron inhibits myogenesis via oxidative stress, leading to an imbalance in skeletal muscle homeostasis. —Ikeda, Y., Satoh, A., Horinouchi, Y., Hamano, H., Watanabe, H., Imao, M., Imanishi, M., Zamami, Y., Takechi, K., Izawa-Ishizawa, Y., Miyamoto, L., Hirayama, T., Nagasawa, H., Ishizawa, K., Aihara, K.-I., Tsuchiya, K., Tamaki, T. Iron accumulation causes impaired myogenesis correlated with MAPK signaling pathway inhibition by oxidative stress. FASEB J. 33, 9551–9564 (2019). www.fasebj.org.

Original languageEnglish
Pages (from-to)9551-9564
Number of pages14
JournalFASEB Journal
Volume33
Issue number8
DOIs
Publication statusPublished - Aug 1 2019
Externally publishedYes

Keywords

  • ERK1/2
  • muscle differentiation
  • muscle regeneration
  • p38MAPK

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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