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Iron accumulation causes impaired myogenesis correlated with MAPK signaling pathway inhibition by oxidative stress
Author(s) -
Ikeda Yasumasa,
Satoh Akiho,
Horinouchi Yuya,
Hamano Hirofumi,
Watanabe Hiroaki,
Imao Mizuki,
Imanishi Masaki,
Zamami Yoshito,
Takechi Kenshi,
IzawaIshizawa Yuki,
Miyamoto Licht,
Hirayama Tasuku,
Nagasawa Hideko,
Ishizawa Keisuke,
Aihara KenIchi,
Tsuchiya Koichiro,
Tamaki Toshiaki
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201802724rr
Subject(s) - myogenesis , skeletal muscle , c2c12 , myocyte , oxidative stress , muscle atrophy , chemistry , medicine , endocrinology , microbiology and biotechnology , regeneration (biology) , biology
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