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STUDY OF THE PHENOTYPES AND FUNCTIONS OF TRP FAMILY MEMBERS EXPRESSED IN NEURONS

Research Project

Project/Area Number 15590059
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKyoto University

Principal Investigator

KANEKO Shuji  Kyoto University, Graduate School of Pharmaceutical Sciences, Professor, 薬学研究科, 教授 (60177516)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsTRPC5 / TRPC4 / TRPM2 / siRNA / Xenopus oocytes / primary culture neuron / cerebral cortex / hydrogen peroxide / ADPリボース / 受容体活性化型カチオンチャネル / Ca^<2+>流入 / RNA干渉法 / TRPチャネル / 活性酸素 / 神経細胞死 / カルシウム / ラジカルストレス / RNAi
Research Abstract

(1) A brief exposure to hydrogen peroxide (H_2O_2) induces severe deterioration of primary cultured neurons in vitro. We have investigated a possible link between the H_2O_2-induced neuronal death and Ca^<2+>-permeable TRPM2 channels that are supposed to be regulated by ADP-ribose (ADPR) and/or H_2O_2. In most of cultured cerebral cortical neurons from fetal rat, TRPM2 proteins were detected at cell bodies immunocytochemically. Application of H_2O_2 to cultured neurons elicited an increase in intracellular Ca^<2+> concentration ([Ca^<2+>]_i) caused by Ca^<2+> influx and subsequent neuronal death in a similar concentration range. Molecular cloning of rat TRPM2 cDNA revealed several differences in amino acid sequences within Nudix box region as compared with those of human and mouse TRPM2. ADPR-induced current responses, H_2O_2-induced Ca^<2+> influx and H_2O_2-induced cell death were elicited in human embryonic kidney cells heterogeneously expressing rat TRPM2. Treatment of cultured neurons with small interfering RNA (siRNA) against rat TRPM2 caused decrease in immunoreactive TRPM2 content and the H_2O_2-induced Ca^<2+> influx. Moreover, H_2O_2-induced neuronal death was significantly inhibited by the siRNA treatment. These results suggest a critical role of TRPM2 in regulation of neuronal survival as well as the intracellular Ca^<2+> homeostasis.
(2)In cultured cerebral cortical neurons from feral rat, TRPC1,3,4,5 and 6 proteins are detected by immunocytochemistry. In Fura-2 loaded neurons, Ca^<2+> influx was observed after P2Y receptor stimulation with ATP, which was inhibited by La^<3+>, Zn^<2+> and SKF96365. Both TRPC3 immunoreactivity and the receptor-activated Ca^<2+> influx were decreased in the neurons treated with anti-TRPC3 antisense oligodeoxynucleotide. There results suggest that TRPC3 channels are involved in the receptor-operated Ca^<2+> influx in immature cerebral cortical neurons.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (21 results)

All 2005 2004 2003

All Journal Article (21 results)

  • [Journal Article] Scallop DMT functions as a Ca^<2+> transporter2005

    • Author(s)
      H.Toyohara et al.
    • Journal Title

      FEBS Letters 579

      Pages: 2727-2730

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inhibition of TRPC5 channels by Ca^<2+>-binding protein 1 in Xenopus oocytes2005

    • Author(s)
      M.Kinoshita-Kawada et al.
    • Journal Title

      Pflugers Archive European Journal of Physiology (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Scallop DMT functions as a Ca^<2+> transporter.2005

    • Author(s)
      Haruhiko Toyohara et al.
    • Journal Title

      FEBS Lett. 579

      Pages: 2727-2730

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 「研究成果報告書概要(欧文)」より2005

    • Author(s)
      Mariko Kinoshita-Kawada et al.
    • Journal Title

      Pflugers Archive European Journal of Physiology (in press)

    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inhibition of TRPC5 channels by Ca^<2+> binding protein 1 in Xenopus oocytes2005

    • Author(s)
      M.Kinoshita-Kawada et al.
    • Journal Title

      Pflugers Archive European Journal of Physiology (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of scallop DMT as a metal transporter responsible for cadmium accumulation2005

    • Author(s)
      H.Toyohara et al.
    • Journal Title

      FEBS Letters (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] α-Tocotrienol provides the most potent neuroprotection among vitamin E analogs on cultured striatal neurons2004

    • Author(s)
      F.Osakada et al.
    • Journal Title

      Neuropharmacology 47

      Pages: 904-915

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mechanisms of oxygen glucose deprivation-induced goutamate release from cerebrocortical slice cultures2004

    • Author(s)
      S.Fujimoto et al.
    • Journal Title

      Neuroscience Research 50

      Pages: 179-187

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 「研究成果報告書概要(欧文)」より2004

    • Author(s)
      Shinji Fujimoto et al.
    • Journal Title

      Neurosci.Res. 50

      Pages: 179-187

    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 「研究成果報告書概要(欧文)」より2004

    • Author(s)
      Feng Wang et al.
    • Journal Title

      J.Pharmacol.Exp.Ther. 308

      Pages: 120-126

    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mechanisms of oxygen glucose deprivation-induced glutamate release from cerebrocortical slice cultures2004

    • Author(s)
      Fujimoto et al.
    • Journal Title

      Neuroscience Research 50

      Pages: 179-187

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Neuroprotective effects of α-tocopherol on oxidative stress in rat striatal cultures2003

    • Author(s)
      F.Osakada et al.
    • Journal Title

      European Journal of Pharmacology 65

      Pages: 15-22

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dopamine is involved in selectivity of dopaminergic neuronal death by rotenone2003

    • Author(s)
      N.Sakka et al.
    • Journal Title

      NeuroReport 14

      Pages: 2425-2428

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Serofendic acid prevents acute glutamate neurotoxicity in cultured cortical neurons2003

    • Author(s)
      R.Taguchi et al.
    • Journal Title

      European Journal of Pharmacology 477

      Pages: 195-203

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Nicotinic acetylcholine receptor-mediated neuroprotection by donepezil against gultamate neurotoxicity in rat cortical neurons2003

    • Author(s)
      Y.Takada et al.
    • Journal Title

      The Journal of Pharmacology and Experimental Therapeutics 306

      Pages: 772-777

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dopamine is involved in selectivity of dopaminergic neuronal death by rotenone.2003

    • Author(s)
      Noriko Sakka et al.
    • Journal Title

      Neuroreport 14

      Pages: 2425-2428

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Nicotinic acetylcholine receptor-mediated neuroprotection by donepezil against glutamate neurotoxicity in rat cortical neurons.2003

    • Author(s)
      Yuki Takada et al.
    • Journal Title

      J.Pharmacol.Exp.Ther. 306

      Pages: 772-777

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 「研究成果報告書概要(欧文)」より2003

    • Author(s)
      Haruki Shibata et al.
    • Journal Title

      J.Neurochem 86

      Pages: 1201-1212

    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Serofendic acid prevents acute glutamate neurotoxicity in cultured cortical neurons.2003

    • Author(s)
      Ryota Taguchi et al.
    • Journal Title

      Eur.J.Pharmacol. 477

      Pages: 195-203

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] N-methyl-D-aspartate receptors contribute to the maintenance of dopaminergic neurons in rat midbrain slice cultures.2003

    • Author(s)
      Hiroshi Katsuki et al.
    • Journal Title

      Neurosci.Lett. 341

      Pages: 123-126

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 「研究成果報告書概要(欧文)」より2003

    • Author(s)
      Fumitaka Osakada et al.
    • Journal Title

      Eur.J.Pharmacol. 465

      Pages: 15-22

    • Related Report
      2004 Final Research Report Summary

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Published: 2003-04-01   Modified: 2016-04-21  

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