Additional effects of simultaneous treatment with C14-Cblin and celastrol on the clinorotation-induced rat L6 myotube atrophy

Kanako Kitahata, Takayuki Uchida, Runa Taniguchi, Ayano Kato, Kosuke Sugiura, Iori Sakakibara, Motoko Oarada, Tomoya Fukawa, Park Junsoo, Choi Inho, Takeshi Nikawa

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1 Citation (Scopus)


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 C14-Cblin 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 C14-Cblin 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.

Original languageEnglish
Pages (from-to)127-134
Number of pages8
JournalJournal of Medical Investigation
Issue number1.2
Publication statusPublished - 2022

Bibliographical note

Funding Information:
This work supported by R. Nakao and A. Ochi at Tokushima University, T. Hashizume at Advanced Engineering Services and A. Higashibata at Japan Aerospace Exploration Agency.

Funding Information:
This work was supported by a Grant-in-Aid for Scientific Research (Kakenhi 19H04054) from the Ministry of Education, Science and Culture, Japan, and Japan Aerospace Exploration Agency (JAXA).

Publisher Copyright:
© 2022, University of Tokushima. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)


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