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ID 109380
タイトル別表記
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。
著者
越智, ありさ 徳島大学大学院栄養生命科学教育部(人間栄養科学専攻)
安倍, 知紀 The University of Tokushima KAKEN研究者をさがす
中尾, 玲子 The University of Tokushima|National Institute of Advanced Industrial Science and Technology 徳島大学 教育研究者総覧 KAKEN研究者をさがす
Yamamoto, Yoriko The University of Tokushima
Kitahata, Kanako The University of Tokushima
Takagi, Marina The University of Tokushima
平坂, 勝也 The University of Tokushima KAKEN研究者をさがす
Ohno, Ayako The University of Tokushima
Taesik, Gwag Yonsei University
Choi, Inho Yonsei University
Kawamura, Tomoyuki The University of Tokushima
キーワード
Cbl-b
IRS-1
Mice
Skeletal muscle atrophy
Ubiquitin ligase inhibitor
資料タイプ
学位論文
抄録
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.
掲載誌名
Archives of Biochemistry and Biophysics
ISSN
00039861
10960384
cat書誌ID
AA00547159
AA11539811
出版者
Elsevier
570
開始ページ
23
終了ページ
31
発行日
2015-02-14
備考
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨 : LID201505251025.pdf
論文本文 : k2850_fulltext.pdf
本論文は,著者Arisa Ochiの学位論文として提出され, 学位審査・授与の対象となっている。
著者の申請により要約(2015-05-26公開)に替えて論文全文を公開(2020-04-20)
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第2850号
学位記番号
甲栄第228号
学位授与年月日
2015-03-23
学位名
博士(栄養学)
学位授与機関
徳島大学
部局
医学系
薬学系
生物資源系