A Critical Role of TRPM2 in Neuronal Cell Death by Hydrogen Peroxide
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概要
- 論文の詳細を見る
A brief exposure to hydrogen peroxide (H2O2) induces severe deterioration of primary cultured neurons in vitro. We have investigated a link between the H2O2-induced neuronal death and Ca2+-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 H2O2 to the cultured neurons elicited an increase in intracellular Ca2+ concentration ([Ca2+]i) caused by Ca2+ influx and the Ca2+-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, H2O2-induced Ca2+ influx, and H2O2-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 H2O2-induced Ca2+ influx, significantly inhibited H2O2-induced neuronal death. These results suggest that TRPM2 plays a pivotal role in H2O2-induced neuronal death as redox-sensitive Ca2+-permeable channels expressed in neurons.
- 社団法人 日本薬理学会の論文
- 2006-05-20
著者
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Katsuki Hiroshi
Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto
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Kume Toshiaki
京都大学 薬学研究科生体機能解析学
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Kume Toshiaki
京都大学 薬学研究科薬品作用解析学分野
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Kume Toshiaki
京都大学 薬学研究科薬品作用解析学
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Kume Toshiaki
同志社女子大学 医療薬学科薬理学
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Kume Toshiaki
Department Of Pharmaceutical Science Kyoto University Graduate School Of Pharmacology
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Takada-takatori Yuki
京都大学 薬学研究科薬品作用解析学
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Akaike A
Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Kyoto University
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Akaike Akinori
京都大学 薬学研究科生体機能解析学
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Akaike Akinori
京都薬科大学 病態生理
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Akaike Akinori
Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Kyoto University
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Kume Toshiaki
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Kyoto University
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KANEKO Shuji
Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University
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Hara Yuji
Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Kyoto University
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Hara Yuji
Center For Integrative Bioscience Okazaki National Research Institutes
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MORI Yasuo
Laboratory of Molecular Biology, Department of Synthetic and Biological Chemistry, Graduate School o
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Honda Y
Department Of Ophthalmology And Visual Sciences Graduate School Of Medicine Kyoto University
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Akaike Akinori
Department Of Pharmaceutical Science Kyoto University Graduate School Of Pharmacology
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KAWAKAMI Seiko
Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University
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HARA Yuji
Laboratory of Molecular Biology, Graduate School of Engineering, Kyoto University
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WAKAMORI Minoru
Laboratory of Molecular Biology, Graduate School of Engineering, Kyoto University
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ITOH Etsuko
Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University
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MINAMI Toshiyuki
Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University
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TAKADA Yuki
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University
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Wakamori Minoru
Laboratory Of Molecular Biology Graduate School Of Engineering Kyoto University
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Kaneko Satoshi
Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Kyoto University
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Itoh Etsuko
Department Of Molecular Pharmacology Graduate School Of Pharmaceutical Sciences Kyoto University
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Takada Yuki
Department Of Applied Chemistry And Bio Engineer Ing Graduate School Of Engineering Osaka City Unive
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Kawakami Seiko
Department Of Molecular Pharmacology Graduate School Of Pharmaceutical Sciences Kyoto University
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Kaneko Shuji
Department Of Applied Biological Chemistry Graduate School Of Agricultural Science Kobe University
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Tochikawa Yoshinaga
Institute Of Research And Development Fujimoto Pharmaceutical Corporation
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Katsuki Hiroshi
Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences The University Of Tokyo
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Takada-takatori Yuki
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Doshisha Women's College
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Akaike Akinori
Dep. Of Pharmacology Graduate School Of Pharmaceutical Sciences Kyoto Univ. Jpn
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Katsuki Hiroshi
Department Of Chemico-pharmacological Sciences Graduate School Of Pharmaceutical Sciences Kumamoto U
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Minami Toshiyuki
Department Of Molecular Pharmacology Graduate School Of Pharmaceutical Sciences Kyoto University
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Mori Yasuo
Laboratory Of Molecular Biology Graduate School Of Engineering Kyoto University
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Mori Yasuo
Laboratory Of Food Chemistry Faculty Of Fisheries Kagoshima University
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Kume T
Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Kyoto University
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Akaike Akinori
Department of Neuropharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
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Hara Yuji
Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University
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