論文

査読有り 筆頭著者 責任著者
2012年9月

Cyclooxygenase-Independent Neuroprotective Effects of Aspirin Against Dopamine Quinone-Induced Neurotoxicity

Neurochemical Research
  • Masato Asanuma
  • ,
  • Ikuko Miyazaki
  • ,
  • Yuri Kikkawa
  • ,
  • Naotaka Kimoto
  • ,
  • Mika Takeshima
  • ,
  • Shinki Murakami
  • ,
  • Ko Miyoshi

37
9
開始ページ
1944
終了ページ
1951
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s11064-012-0813-2
出版者・発行元
SPRINGER/PLENUM PUBLISHERS

Prostaglandin H synthase exerts not only cyclooxygenase activity but also peroxidase activity. The latter activity of the enzyme is thought to couple with oxidation of dopamine to dopamine quinone. Therefore, it has been proposed that cyclooxygenase inhibitors could suppress dopamine quinone formation. In the present study, we examined effects of various cyclooxygenase inhibitors against excess methyl L-3,4-dihydroxyphenylalanine (L-DOPA)-induced quinoprotein (protein-bound quinone) formation and neurotoxicity using dopaminergic CATH.a cells. The treatment with aspirin inhibited excess methyl L-DOPA-induced quinoprotein formation and cell death. However, acetaminophen did not show protective effects, and indomethacin and meloxicam rather aggravated these methyl L-DOPA-induced changes. Aspirin and indomethacin did not affect the level of glutathione that exerts quenching dopamine quinone in dopaminergic cells. In contrast with inhibiting effects of higher dose in the previous reports, relatively lower dose of aspirin that affected methyl L-DOPA-induced quinoprotein formation and cell death failed to prevent cyclooxygenase-induced dopamine chrome generation in cell-free system. Furthermore, aspirin but not acetaminophen or meloxicam showed direct dopamine quinone-scavenging effects in dopamine-semiquinone generating systems. The present results suggest that cyclooxygenase shows little contribution to dopamine oxidation in dopaminergic cells and that protective effects of aspirin against methyl L-DOPA-induced dopamine quinone neurotoxicity are based on its cyclooxygenase-independent property.

リンク情報
DOI
https://doi.org/10.1007/s11064-012-0813-2
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000307280100013&DestApp=WOS_CPL
ID情報
  • DOI : 10.1007/s11064-012-0813-2
  • ISSN : 0364-3190
  • eISSN : 1573-6903
  • Web of Science ID : WOS:000307280100013

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