N-Myristoylated ubiquitin ligase Cbl-b inhibitor prevents on glucocorticoid-induced atrophy in mouse skeletal muscle

• Material Type: 博士論文
• Title: N-Myristoylated ubiquitin ligase Cbl-b inhibitor prevents on glucocorticoid-induced atrophy in mouse skeletal muscle
• Author/Editor: Ochi, Arisa; Abe, Tomoki; Nakao, Reiko; Yamamoto, Yoriko; Kitahata, Kanako; Takagi, Marina; Hirasaka, Katsuya; Ohno, Ayako; Teshima-Kondo, Shigetada; Taesik, Gwag; Choi, Inho; Kawamura, Tomoyuki; Nemoto, Hisao; Mukai, Rie; Terao, Junji; Nikawa, Takeshi
• Author Heading: Ochi, Arisa; Abe, Tomoki; Nakao, Reiko; Yamamoto, Yoriko; Kitahata, Kanako; Takagi, Marina; Hirasaka, Katsuya; Ohno, Ayako; Teshima-Kondo, Shigetada; Taesik, Gwag; Choi, Inho; Kawamura, Tomoyuki; Nemoto, Hisao; Mukai, Rie; Terao, Junji; Nikawa, Takeshi
• Publication, Distribution, etc.: Elsevier
• Publication Date: 2015-02-14
• Publication Date (W3CDTF): 2015-02-14
• Alternative Title: Ｎ末端へミリストイル化を施したCbl-bユビキチン化活性阻害剤は、グルココルチコイド誘導性の筋萎縮を抑制する。
• Periodical title: Archives of Biochemistry and Biophysics
• No. or year of volume/issue: 570
• Volume: 570
• Pages: 23-31
• ISSN (Periodical Title): ISSN : 0003-9861; ISSN : 1096-0384
• Degree grantor/type: 徳島大学
• Date Granted: 2015-03-23
• Dissertation Number: 甲第2850号
• Degree Type: 博士（栄養学）
• Text Language Code: eng
• Subject Heading: Cbl-b; IRS-1; Mice; Skeletal muscle atrophy; Ubiquitin ligase inhibitor
• Target Audience: 一般
• Note (General): A DGpYMP peptide mimetic of tyrosine608-phosphorylated insulin receptor substrate-1 (IRS-1), named Cblin, was previously shown to significantly inhibit Cbl-b-mediated IRS-1 ubiquitination. In the present study, we developed N-myristoylated Cblin and investigated whether it was effective in preventing glucocorticoid-induced muscle atrophy. Using HEK293 cells overexpressing Cbl-b, IRS-1 and ubiquitin, we showed that the 50% inhibitory concentrations of Cbl-b-mediated IRS-1 ubiquitination by N-myristoylated Cblin and Cblin were 30 and 120 μM, respectively. Regarding the DEX-induced atrophy of C2C12 myotubes, N-myristoylated Cblin was more effective than Cblin for inhibiting the DEX-induced decreases in C2C12 myotube diameter and IRS-1 degradation. The inhibitory efficacy of N-myristoylated Cblin on IRS-1 ubiquitination in C2C12 myotubes was approximately fourfold larger than that of Cblin. Furthermore, N-myristoylation increased the incorporation of Cblin into HEK293 cells approximately 10-folds. Finally, we demonstrated that N-myristoylated Cblin prevented the wet weight loss, IRS-1 degradation, and MAFbx/atrogin-1 and MuRF-1 expression in gastrocnemius muscle of DEX-treated mice approximately fourfold more effectively than Cblin. Taken together, these results suggest that N-myristoylated Cblin prevents DEX-induced skeletal muscle atrophy in vitro and in vivo, and that N-myristoylated Cblin more effectively prevents muscle atrophy than unmodified Cblin.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1016/j.abb.2015.02.006
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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