Inhibitory effects of local anesthetics on the proteasome and their biological actions

Permalink : https://repository.lib.tottori-u.ac.jp/8152

フルテキストファイル	sr7_s41598-017-04652-2.pdf 4.2 MB
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	https://www.nature.com/articles/s41598-017-04652-2
ISSN	20452322
掲載誌名	SCIENTIFIC REPORTS
最新掲載誌名	SCIENTIFIC REPORTS
巻	7
発行日	2017-07-11
出版者DOI	10.1038/s41598-017-04652-2
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