2017年7月
Inhibitory effects of local anesthetics on the proteasome and their biological actions
SCIENTIFIC REPORTS
- 巻
- 7
- 号
- 1
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/s41598-017-04652-2
- 出版者・発行元
- NATURE PUBLISHING GROUP
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 beta 5 subunit of the 20S proteasome, and not to the other active subunits, beta 1 and beta 2. 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 p53positive but not of p53-negative cancer cells.
- リンク情報
-
- DOI
- https://doi.org/10.1038/s41598-017-04652-2
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000405172600046&DestApp=WOS_CPL
- URL
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85023203681&origin=inward
- URL
- http://orcid.org/0000-0003-1919-6309
- ID情報
-
- DOI : 10.1038/s41598-017-04652-2
- ISSN : 2045-2322
- ORCIDのPut Code : 46070441
- SCOPUS ID : 85023203681
- Web of Science ID : WOS:000405172600046