Iron accumulation causes impaired myogenesis correlated with MAPK signaling pathway inhibition by oxidative stress
Iron accumulation causes impaired myogenesis correlated with MAPK signaling pathway inhibition by oxidative stress
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DOI：
10.1096/fj.201802724rr
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发表时间：
2019-08-01
期刊：
影响因子：
4.8
通讯作者：
Tamaki, Toshiaki
中科院分区：
文献类型：
--
作者：
Ikeda, Yasumasa;Satoh, Akiho;Tamaki, Toshiaki
骨骼肌萎缩是由各种病理生理条件下肌肉变性和再生的稳态平衡破坏引起的。我们以前曾报道，铁积累诱导骨骼肌萎缩通过泛素连接酶依赖性途径。然而，铁积累对肌肉再生的潜在影响仍不清楚。为了研究铁积累对肌生成的影响，我们使用了心脏毒素（CTX）诱导的肌肉再生的小鼠模型在体内和C2 C12小鼠成肌细胞在体外。在铁超载的小鼠中，骨骼肌表现出氧化应激增加和卫星细胞标志物表达减少。在CTX诱导的肌肉损伤后，这些小鼠还表现出延迟的肌肉再生，再生肌纤维的尺寸减小，成肌细胞分化标志物的表达减少，以及MAPK信号通路的磷酸化减少。在体外，铁超载也抑制了C2 C12成肌细胞的分化，但抑制可以逆转超氧阴离子清除使用tempol。过量的铁通过氧化应激抑制肌生成，导致骨骼肌稳态失衡。Ikeda，Y.，Satoh，A.，Horinouchi，Y.，Hamano，H.，渡边，H.，Imao，M.，Imanishi，M.，Zamami，Y.，Takechi，K.，Izawa-Ishizawa，Y.，Miyamoto，L.，Hirayama，T.，Nagasawa，H.，Ishizawa，K.，Aihara，K.-一、Tsuchiya，K.，Tamaki，T.铁蓄积导致与氧化应激抑制MAPK信号通路相关的肌生成受损。
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.