論文

査読有り
2015年5月

Histone deacetylase inhibitor attenuates neurotoxicity of clioquinol in PC12 cells

TOXICOLOGY
  • Takao Fukui
  • ,
  • Kunihiko Asakura
  • ,
  • Chika Hikichi
  • ,
  • Tomomasa IshikaWa
  • ,
  • Rie Murai
  • ,
  • Seiko Hirota
  • ,
  • Ken-ichiro Murate
  • ,
  • MadOko Kizawa
  • ,
  • Akihiro Ueda
  • ,
  • Shinji Ito
  • ,
  • Tatsuro Mutoh

331
開始ページ
112
終了ページ
118
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.tox.2015.01.013
出版者・発行元
ELSEVIER IRELAND LTD

Clioquinol is considered to be a causative agent of subacute myelo-optico neuropathy (SMON), although the pathogenesis of SMON is yet to be elucidated. We have previously shown that clioquinol inhibits nerve growth factor (NGF)-induced Trk autophosphorylation in PC12 cells transformed with human Trk cDNA. To explore the further mechanism of neuronal damage by clioquinol, we evaluated the acetylation status of histones in PC12 cells. Clioquinol reduced the level of histone acetylation, and the histone deacetylase (HDAC) inhibitor Trichostatin A upregulated acetylated histones and prevented the neuronal cell damage caused by clioquinol. In addition, treatment with HDAC inhibitor decreased neurite retraction and restored the inhibition of NGF-induced Trk autophosphorylation by clioquinol. Thus, clioquinol induced neuronal cell death via deacetylation of histones, and HDAC inhibitor alleviates the neurotoxicity of clioquinol. Clioquinol is now used as a potential medicine for malignancies and neurodegenerative diseases. Therefore, HDAC inhibitors can be used as a candidate medicine for the prevention of its side effects on neuronal cells. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Web of Science ® 被引用回数 : 5

リンク情報
DOI
https://doi.org/10.1016/j.tox.2015.01.013
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000354591600010&DestApp=WOS_CPL

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