ID 8152
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Authors
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 Researchers DB KAKEN
Kato, Masaru Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University Researchers DB 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 Researchers DB KAKEN
Itoh, Toshiyuki Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University Researchers DB KAKEN
Ninomiya, Haruaki Department of Biological Regulation, Tottori University Researchers DB KAKEN
Hisatome, Ichiro Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University Researchers DB KAKEN
Morimoto, Yukio Research Reactor Institute, Kyoto University
Keywords
Kososan
Recurrent depression
Social defeat stress
Antidepressant
Abstract
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.
Publisher
Springer Nature
Content Type
Journal Article
Link
ISSN
20452322
Journal Title
SCIENTIFIC REPORTS
Current Journal Title
SCIENTIFIC REPORTS
Volume
7
Published Date
2017-07-11
Publisher-DOI
Text Version
Publisher
Rights
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/.
Citation
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
Department
Faculty of Medicine/Graduate School of Medical Sciences/University Hospital
Language
English
Web of Science Key ut
WOS:000405172600046