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

• Material Type: 博士論文
• ISSN: 0003-9861
• Title: N-Myristoylated ubiquitin ligase Cbl-b inhibitor prevents on glucocorticoid-induced atrophy in mouse skeletal muscle
• Volume: 570
• 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
• Degree grantor/type: 徳島大学
• Date Granted: 2015-03-23
• Date Granted (W3CDTF): 2015-03-23
• Dissertation Number: 甲第2850号
• Degree Type: 博士（栄養学）
• Conferring No. (Dissertation): 甲第2850号
• 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.
• DOI: info:doi/10.1016/j.abb.2015.02.006; https://doi.org/info:doi/10.1016/j.abb.2015.02.006
• Persistent ID (NDL): info:ndljp/pid/11490038; https://dl.ndl.go.jp/pid/11490038
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2020-05-25T09:38:44+09:00
• Format (IMT): application/pdf
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• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/109380
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