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新規低分子量生理活性物質による神経幹細胞の分化制御

Research Project

Project/Area Number 15659059
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionKyoto University

Principal Investigator

赤池 昭紀  京都大学, 薬学研究科, 教授 (80135558)

Co-Investigator(Kenkyū-buntansha) 香月 博志  京都大学, 薬学研究科, 助教授 (40240733)
久米 利明  京都大学, 薬学研究科, 助手 (10303843)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsセロフェンド酸 / アストロサイト / サイクリックAMP / 細胞分化 / チロシンヒドロキシラーゼ / 酪酸 / グルタミン酸トランスポータ / 星状化 / 細胞骨格
Research Abstract

中枢神経細胞およびグリア細胞の機能分化に対する低分子量化合物の作用について検討した。1.神経芽腫細胞株であるSH-SY5Y細胞にdibutyryl cyclic AMP(dbcAMP)あるいはレチノイン酸を処置すると、いずれの場合も突起の伸展を特徴とするニューロン様の細胞形態への変化とともに、チロシンヒドロキシラーゼ(TH)の発現誘導が認められた。TH発現誘導効果はdbcAMPの方がより顕著であり、またノルアドレナリン産生量はdbcAMP処置によって顕著に増大したのに対し,レチノイン酸処置によっては変化しなかった。dbcAMPのTH発現増大作用は、プロテインキナーゼA阻害薬によって部分的に抑制された。また、dbcAMPの細胞内での分解によって生じると考えられる酪酸を処置することによってもTH陽性細胞数の増加とノルアドレナリン産生量の増加が誘導されたが、細胞の形態変化は誘導されなかった。以上のことから、dbcAMPによるSH-SY5Y細胞のノルアドレナリン産生細胞への分化にはプロテインキナーゼAの活性化と酪酸の産生の両者が介在することが示唆された。2.我々が新規に同定した神経保護活性化合物セロフェンド酸は、培養アストロサイトに適用するとdbcAMPによって誘導される形態変化を促進する。この時のアストロサイトでのグルタミン酸トランスポータの発現について検討したところ、セロフェンド酸はdbcAMPによって誘導されるGLT-1およびGLASTの免疫反応性の増大をさらに増強することが明らかになった。したがって、セロフェンド酸はニューロンに対する細胞保護作用を有するだけでなく、グリア細胞の機能分化をも制御する多機能性の内在性化合物であることが示唆された。

Report

(2 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (30 results)

All 2004 Other

All Journal Article (12 results) Publications (18 results)

  • [Journal Article] Excitotoxic degeneration of hypothalamic orexin neurons in slice culture.2004

    • Author(s)
      Katsuki A, Akaike A.
    • Journal Title

      Neurobiology of Disease 15・1

      Pages: 61-69

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Neuronal nitric oxide synthase is crucial for ganglion cell death in rat retinal explant cultures.2004

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

      Journal of Phamacological Sciences 94・1

      Pages: 77-80

    • NAID

      130000073887

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Serofendic acid, a sulfur-containing diterpenoid derived from fetal calf serum, attenuates reactive oxygen species-induced oxidative stress in cultured striatal neurons.2004

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

      Journal of Phamacology and Experimental Therapeutics 311・1

      Pages: 51-59

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mechanisms of oxygen glucose deprivation-induced glutamate release from cerebrocortical slice cultures.2004

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

      Neuroscience Research 50・2

      Pages: 179-187

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Endogenous D-serine is involved in induction of neuronal death induced by N-methyl-D-aspartate and simulated ischemia in rat cerebrocortical slices.2004

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

      Journal of Pharmacology and Experimental Therapeutics 311・2

      Pages: 836-844

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

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

      Neuropharmacology 47・6

      Pages: 904-915

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Proteasome mediates dopaminergic neuronal degeneration, and its inhibition causes α-synuclein inclusions.2004

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

      Journal of Biological Chemistry 279・11

      Pages: 10710-10719

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effects of mitochondrial dysfunction on glutamate receptor-mediated neurotoxicity in cultured rat spinal motor neurons.2004

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

      Brain Research 1015・1-3

      Pages: 73-81

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Endogenous factors regulating neuronal death induced by radical stress.2004

    • Author(s)
      Kume T et al.
    • Journal Title

      Biological and Pharmaceutical Bulletin 27・7

      Pages: 964-967

    • NAID

      110003608896

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Pharmacological characteristics of rotational behavior in hemiparkinsonian rats transplanted with mouse embryonic stem cell-derived neurons.2004

    • Author(s)
      Inden M.et al.
    • Journal Title

      Journal of Pharmacological Sciences 96・1

      Pages: 53-64

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ドネペジルのニコチニックアセチルコリン受容体への作用2004

    • Author(s)
      赤池昭紀, 久米利明
    • Journal Title

      脳21 7・2

      Pages: 59-63

    • Related Report
      2004 Annual Research Report
  • [Journal Article] セロフェンド酸-新規な内在性神経保護物質2004

    • Author(s)
      赤池昭紀, 久米利明
    • Journal Title

      脳21 7・4

      Pages: 87-92

    • Related Report
      2004 Annual Research Report
  • [Publications] Takahata, K. et al.: "Protective effects of selegiline and desmethylselegiline against N-methyl-D-aspartate-induced retinal damage."Eur.J.Pharmacol.. 458(1-2). 81-89 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakamizo, T. et al.: "Phosphodiesterase inhibitors are neuroprotective to cultured spinal motor neurons."J.Neurosci.Res.. 71(4). 485-495 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Osakada, F. et al.: "Neuroprotective effecrts of α-tocopherol on oxidative stress in rat striatal cultures."Eur.J.Pharmacol.. 465(1-2). 15-22 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takahata, K. et al.: "Retinal neronal death induced by intraocular administration of a nitric oxide donor and its rescue by neurotrophic factors in rats."Invest.Ophthalmol.Vis.Sci.. 44(4). 1760-1766 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Katsuki, H. et al.: "N-methyl-D-aspartate receptors contribute to the maintenance of dopaminergic neurons in midbrain sauce cultures."Neurosci.Lett.. 341(2). 123-126 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takada, Y. et al.: "Nicotinic acetyicholine receptor-mediated neuroprotection by donepezil against glutamate neurotoxicitv in rat cortical neurons."J.Pharmacol.Exp.Ther.. 306(2). 772-777 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shibata, H. et al.: "Lipopolysaccharide-induced dopaminergic cell death in rat midbrain slice cultures : role of inducible nitric oxide synthase and protection by indomethacin."J.Neurochem.. 86(5). 1201-1212 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takahata, K. et al.: "Retinal neurotoxicity of nitric oxide donors with different half-life of nitric oxide release : Involvement of N-methyl-D-aspartate receptors."J.Pharmacol.Sci.. 92(4). 428-432 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Taguchi, R. et al.: "Serofendic acid prevents acute glutamate neurotoxicity in cultured cortical neurons."Eur.J.Pharmacol.. 477(3). 195-203 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimazu, S. et al.: "Transporter-mediated actions of R-(-)-1-(benzofuran-2-y1)-2-propylaminopentane."Eur.J.Pharmacol.. 482(1-3). 9-16 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sakka, N. et al.: "Dopamine is involved in selectivity of dopaminergic neuronal death by rotenone."Neuroreport. 14(18). 2425-2528 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akaike, A. et al.: "Pharmacological and physiological properties of serofendic acid, a novel neuroprotective substance isolated from fetal calf serum."Life Sci.. 74(2-3). 263-269 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kitamura, Y. et al.: "Hyperbilirubinemia protects against focal ischemia in rats."J.Neurosci.Res.. 71(4). 544-550 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kitamura, Y. et al.: "Neuroprotective mechanisms of antiparkinsonian dopamine D2-receptor subfamily agonists."Neurochem.Res.. 28(7). 1035-1040 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamauchi, T. et al.: "Mitocliondrial ATP-sensjtive potassium channel : a novel site for neuroprotection."Invest.Ophthalmol.Vis.Sci.. 44(6). 2750-2756 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamauchi, T. et al.: "Inhibition of glutamate-induced nitric oxide synthase activation by dopamine in cultured rat retinal neurons."Neurosci.Lett.. 347(3). 155-158 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 赤池昭紀: "セロフェンド酸-胎仔血清から発見された神経保護物質"別冊 医学のあゆみ. 205(13). 1002-1003 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 赤池昭紀: "創薬シーズとしての非タンパク性生理活性物質め探索と薬理作用の解析"Pharma Vision News. 2. 10-13 (2003)

    • Related Report
      2003 Annual Research Report

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

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