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

• 資料種別: 博士論文
• タイトル: N-Myristoylated ubiquitin ligase Cbl-b inhibitor prevents on glucocorticoid-induced atrophy in mouse skeletal muscle
• 著者・編者: 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
• 著者標目: 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
• 出版事項: Elsevier
• 出版年月日等: 2015-02-14
• 出版年（W3CDTF）: 2015-02-14
• 並列タイトル等: 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。
• タイトル（掲載誌）: Archives of Biochemistry and Biophysics
• 巻号年月日等（掲載誌）: 570
• 掲載巻: 570
• 掲載ページ: 23-31
• ISSN（掲載誌）: ISSN : 0003-9861; ISSN : 1096-0384
• 授与機関名: 徳島大学
• 授与年月日: 2015-03-23
• 報告番号: 甲第2850号
• 学位: 博士（栄養学）
• 本文の言語コード: eng
• 件名標目: Cbl-b; IRS-1; Mice; Skeletal muscle atrophy; Ubiquitin ligase inhibitor
• 対象利用者: 一般
• 一般注記: 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.
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: インターネット公開
• 関連情報（DOI）: 10.1016/j.abb.2015.02.006
• 連携機関・データベース: 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
• 提供元機関・データベース: 徳島大学 : 徳島大学機関リポジトリ

目次

http://repo.lib.tokushima-u.ac.jp/files/public/10/109380/20170929143830967837/LID201505251025.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/10/109380/20200420100519461020/k2850_fulltext.pdf fulltext