Irisin prevents dexamethasone-induced atrophy in C2C12 myotubes
Irisin prevents dexamethasone-induced atrophy in C2C12 myotubes
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DOI：
10.1007/s00424-020-02367-4
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发表时间：
2020-03-26
影响因子：
4.5
通讯作者：
Kong, In Deok
中科院分区：
文献类型：
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作者：
Chang, Jae Seung;Kong, In Deok
鸢尾素是一种主要由骨骼肌分泌的肌因子，已知其通过增强能量消耗和胰岛素敏感性而具有有益的代谢作用。研究表明，鸢尾素也作为一种自分泌/旁分泌，以促进肌生成和肌肉生长。然而，鸢尾素对肌肉萎缩的保护作用仍不清楚。我们在体外模拟运动模型中证实了电脉冲刺激能上调鸢尾素的分泌.接下来，我们测试了鸢尾素是否对用地塞米松（DEX）（肌肉萎缩的代表性诱导剂）处理的培养的C2 C12肌管发挥抗萎缩作用。用DEX处理培养的肌管减小了肌管的尺寸，增加了蛋白酶体的活性，而这被鸢尾素减弱。此外，鸢尾素有效地防止去磷酸化的叉头盒O（FoxO）3 α和上调的肌肉特异性泛素连接酶在DEX处理的肌管。鸢尾素对DEX介导的肌管萎缩的保护作用部分受胰岛素样生长因子-1依赖性信号的调节。这些结果表明，鸢尾素可能通过抑制FoxO介导的泛素-蛋白酶体过度活性来预防糖皮质激素诱导的肌肉萎缩。
Irisin is a myokine secreted mainly from skeletal muscle that is known for having beneficial metabolic effects via enhancement of energy expenditure and insulin sensitivity. Studies show that irisin also acts as an autocrine/paracrine to promote myogenesis and muscle growth. However, the protective role of irisin against muscular wasting remains unclear. We confirmed that irisin secretion was upregulated by electrical pulse stimulation an in vitro exercise mimetic model. Next, we tested if irisin exerted an anti-atrophic effect on cultured C2C12 myotubes treated with dexamethasone (DEX), a representative inducer of muscular atrophy. Treatment of cultured myotubes with DEX reduced myotube size and increased proteasome activity, which were attenuated by irisin. Also, irisin effectively prevented dephosphorylation of forkhead box O (FoxO) 3 alpha and upregulation of muscle-specific ubiquitin ligases in DEX-treated myotubes. The protective effect of irisin on DEX-mediated myotube atrophy was partially regulated by insulin-like growth factor-1-dependent signaling. These results suggested that irisin may prevent glucocorticoid-induced muscle atrophy by inhibiting FoxO-mediated ubiquitin-proteasome overactivity.