論文

査読有り 筆頭著者
2016年9月

Inhibitory effects of Tyrphostin AG-related compounds on oxidative stress-sensitive transient receptor potential channel activation

EUROPEAN JOURNAL OF PHARMACOLOGY
  • Takahiro Toda
  • ,
  • Shinichiro Yamamoto
  • ,
  • Ryo Yonezawa
  • ,
  • Yasuo Mori
  • ,
  • Shunichi Shimizu

786
開始ページ
19
終了ページ
28
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.ejphar.2016.05.033
出版者・発行元
ELSEVIER SCIENCE BV

Some transient receptor potential (TRP) proteins including TRPA1, TPRM2 and TRPV1 are oxidative stress-sensitive Ca2+-permeable channels. Ca2+ signaling via these TRP channels activated by oxidative stress has been implicated in the aggravation of various inflammatory diseases and pain sensation. We recently reported that Tyrphostin AG490 exerted inhibitory effects on H2O2-induced TRPM2 activation by scavenging the hydroxyl radical. In order to identify stronger inhibitors of oxidative stress-sensitive TRP channels than AG490, we examined the inhibitory effects of Tyrphostin AG-related compounds on H2O2-induced TRP channel activation in human embryonic kidney 293 cells expressing TRP channels. AG555 and AG556 blocked the activation of TRPM2 by H2O2 more strongly than AG490. Regarding TRPV1 and TRPA1, none of the three compounds tested affected H2O2-induced TRPV1 activation; however, AG555 and AG556 reduced H2O2-induced TRPA1 activation more than AG490. Thus, we herein identified AG555 and AG556 as new compounds that exert stronger inhibitory effects on H2O2-induced TRPM2 and TRPA1 activation than AG490. Edaravone, a hydroxyl radical scavenger used in the treatment of cerebral hemorrhage and cerebral infarction, did not affect H2O2-induced TRPM2 or TRPA1 activation. AG555 and AG556 may be useful seed compounds as therapeutic agents for several TRP-related diseases associated with oxidative stress. (C) 2016 Elsevier B.V. All rights reserved.

リンク情報
DOI
https://doi.org/10.1016/j.ejphar.2016.05.033
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27238971
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000380753400003&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.ejphar.2016.05.033
  • ISSN : 0014-2999
  • eISSN : 1879-0712
  • PubMed ID : 27238971
  • Web of Science ID : WOS:000380753400003

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