A Critical Role of TRPM2 in Neuronal Cell Death by Hydrogen Peroxide

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著者

    • WAKAMORI Minoru
    • Laboratory of Molecular Biology, Graduate School of Engineering, Kyoto University
    • ITOH Etsuko
    • Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University
    • MINAMI Toshiyuki
    • Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University
    • TAKADA Yuki
    • Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University
    • KUME Toshiaki
    • Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University
    • KATSUKI Hiroshi
    • Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University
    • MORI Yasuo
    • Laboratory of Molecular Biology, Graduate School of Engineering, Kyoto University
    • AKAIKE Akinori
    • Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

抄録

A brief exposure to hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) induces severe deterioration of primary cultured neurons in vitro. We have investigated a link between the H<sub>2</sub>O<sub>2</sub>-induced neuronal death and Ca<sup>2+</sup>-permeable TRPM2 channels regulated by ADP-ribose (ADPR). In cultured cerebral cortical neurons from fetal rat, TRPM2 proteins were detected at cell bodies and neurite extensions. Application of H<sub>2</sub>O<sub>2</sub> to the cultured neurons elicited an increase in intracellular Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>i</sub>) caused by Ca<sup>2+</sup> influx and the Ca<sup>2+</sup>-dependent neuronal death in a similar concentration range. Molecular cloning of TRPM2 cDNA from rat brain revealed several differences in amino acid sequences within the Nudix box region as compared with those of human and mouse TRPM2. ADPR-induced current responses, H<sub>2</sub>O<sub>2</sub>-induced Ca<sup>2+</sup> influx, and H<sub>2</sub>O<sub>2</sub>-induced cell death were induced in human embryonic kidney cells heterologously expressing rat TRPM2. Treatment of cultured neurons with small interfering RNA against rat TRPM2, which efficiently suppressed immunoreactive TRPM2 content and the H<sub>2</sub>O<sub>2</sub>-induced Ca<sup>2+</sup> influx, significantly inhibited H<sub>2</sub>O<sub>2</sub>-induced neuronal death. These results suggest that TRPM2 plays a pivotal role in H<sub>2</sub>O<sub>2</sub>-induced neuronal death as redox-sensitive Ca<sup>2+</sup>-permeable channels expressed in neurons.<br>

収録刊行物

  • Journal of pharmacological sciences  

    Journal of pharmacological sciences 101(1), 66-76, 2006-05-20 

    The Japanese Pharmacological Society

参考文献:  35件

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各種コード

  • NII論文ID(NAID)
    10018237407
  • NII書誌ID(NCID)
    AA11806667
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    13478613
  • NDL 記事登録ID
    7915769
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  NDL  J-STAGE 
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