Additional effects of simultaneous treatment with C14-Cblin and celastrol on the clinorotation-induced rat L6 myotube atrophy
Additional effects of simultaneous treatment with C14-Cblin and celastrol on the clinorotation-induced rat L6 myotube atrophy
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DOI：
10.2152/jmi.69.127
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发表时间：
2022-02-01
影响因子：
0.7
通讯作者：
Nikawa, Takeshi
中科院分区：
文献类型：
--
作者：
Kitahata, Kanako;Uchida, Takayuki;Nikawa, Takeshi
两种新的试剂，N-肉豆蔻酰化的Cbl-b抑制肽（C14-Cblin）和雷公藤红素，醌甲基化三萜，被报道是有效地防止肌管萎缩。本研究探讨了C14 Cblin和雷公藤红素联合应用对模拟微重力条件下3D旋转诱导的大鼠L 6肌管萎缩的影响。我们首先研究了它们对atrogenes表达的影响。C14-Cblin或雷公藤红素处理显著抑制了3D-旋转引起的MAFbx 1/atrogin-1和MuRF-1的增加，但同时处理没有累加效应。然而，雷公藤红素显着抑制3D-旋转Cbl-b和HSP 70的上调。而3D-旋转降低IRS-1在L 6肌管中的蛋白水平，C14-Cblin和雷公藤红素抑制IRS-1的降解。C14-Cblin和雷公藤红素在微重力条件下也能促进FOXO 3a的磷酸化。同时给予C14 Cblin和雷公藤红素在通过3D-旋转逆转IGF-1信号传导损伤方面几乎没有显示出相加效应。虽然3D-旋转诱导L 6肌管中显著的氧化应激，雷公藤红素抑制3D-旋转诱导的ROS产生。C14-Cblin和雷公藤红素处理组可抑制L 6肌管直径的减小，并增加慢收缩肌细胞蛋白质含量。C14-Cblin和雷公藤红素的同时处理比单一处理附加地防止3D-旋转诱导的肌管萎缩。
Two novel reagents, N-myristoylated Cbl-b inhibitory peptide (C14-Cblin) and celastrol, a quinone methide triterpene, are reported to be effective in preventing myotube atrophy. The combined effects of C14Cblin and celastrol on rat L6 myotubes atrophy induced by 3D-clinorotation, a simulated microgravity model, was investigated in the present study. We first examined their effects on expression in atrogenes. Increase in MAFbx1/atrogin-1 and MuRF-1 by 3D-clinorotation was significantly suppressed by treatment with C14-Cblin or celastrol, but there was no additive effect of simultaneous treatment. However, celastrol significantly suppressed the upregulation of Cbl-b and HSP70 by 3D-clinorotation. Whereas 3D-clinorotation decreased the protein level of IRS-1 in L6 myotubes, C14-Cblin and celastrol inhibited the degradation of IRS-1. C14-Cblin and celastrol promoted the phosphorylation of FOXO3a even in microgravity condition. Simultaneous administration of C14Cblin and celastrol had shown little additive effect in reversing the impairment of IGF-1 signaling by 3D-clinorotation. While 3D-clinorotation-induced marked oxidative stress in L6 myotubes, celastrol suppressed 3D-clinorotation-induced ROS production. Finally, the C14-Cblin and celastrol-treated groups were inhibited decrease in L6 myotube diameter and increased the protein content of slow-twitch MyHC cultured under 3D-clinorotation. The simultaneous treatment of C14-Cblin and celastrol additively prevented 3D-clinorotation-induced myotube atrophy than single treatment.