フルテキストファイル
著者
Bahrudin Udin Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University / Present address: Department of Cardiology and Vascular Medicine, Faculty of Medicine, Diponegoro University
Unno, Masaki Graduate School of Science and Engineering, Ibaraki University / Frontier Research Center for Applied Atomic Sciences, Ibaraki University
Nishio, Kazuya Research Reactor Institute, Kyoto University / Present address: Graduate School of Life Science, University of Hyogo
Kita, Akiko Research Reactor Institute, Kyoto University
Li, Peili Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University 研究者総覧 KAKEN
Kato, Masaru Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University 研究者総覧 KAKEN
Inoue, Masashi Department of Surgery, National Hospital Organization Kure Medical Center
Tsujitani Shunichi Cancer Center, Tottori University Hospital
Murakami, Takuto School of Science and Technology, Kwansei Gakuin University / RIKEN SPring-8 Center, RIKEN Harima Institute
Sugiyama, Rina Graduate School of Science and Engineering, Ibaraki University
Saeki, Yasushi Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science
Obara, Yuji Graduate School of Science and Engineering, Ibaraki University / Frontier Research Center for Applied Atomic Sciences, Ibaraki University
Tanaka, Keiji Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science
Yamaguchi, Hiroshi School of Science and Technology, Kwansei Gakuin University / RIKEN SPring-8 Center, RIKEN Harima Institute
Sakane, Isao Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University
Kawata, Yasushi Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University 研究者総覧 KAKEN
Itoh, Toshiyuki Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University 研究者総覧 KAKEN
Ninomiya, Haruaki Department of Biological Regulation, Tottori University 研究者総覧 KAKEN
Hisatome, Ichiro Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University 研究者総覧 KAKEN
Morimoto, Yukio Research Reactor Institute, Kyoto University
キーワード
Kososan
Recurrent depression
Social defeat stress
Antidepressant
抄録
Local anesthetics (LAs) inhibit endoplasmic reticulum-associated protein degradation, however the mechanisms remain elusive. Here, we show that the clinically used LAs pilsicainide and lidocaine bind directly to the 20S proteasome and inhibit its activity. Molecular dynamic calculation indicated that these LAs were bound to the β5 subunit of the 20S proteasome, and not to the other active subunits, β1 and β2. Consistently, pilsicainide inhibited only chymotrypsin-like activity, whereas it did not inhibit the caspase-like and trypsin-like activities. In addition, we confirmed that the aromatic ring of these LAs was critical for inhibiting the proteasome. These LAs stabilized p53 and suppressed proliferation of p53-positive but not of p53-negative cancer cells.
出版者
Springer Nature
資料タイプ
学術雑誌論文
外部リンク
ISSN
20452322
掲載誌名
SCIENTIFIC REPORTS
最新掲載誌名
SCIENTIFIC REPORTS
7
発行日
2017-07-11
出版者DOI
著者版フラグ
出版社版
著作権表記
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
掲載情報
Bahrudin Udin, Unno Masaki, Nishio Kazuya, et al. Inhibitory effects of local anesthetics on the proteasome and their biological actions. SCIENTIFIC REPORTS. 2017. 7. doi:10.1038/s41598-017-04652-2
部局名
医学部・医学系研究科・医学部附属病院
言語
英語
Web of Science Key ut
WOS:000405172600046