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1998 Fiscal Year Final Research Report Summary

Calcium signal-dependent mechanisms of recovery from neuronal apoptosis

Research Project

Project/Area Number 09672231
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionToyama Medical and Pharmaceutical University

Principal Investigator

TSUDA Masaki  Toyama Medical and Pharmaceutical University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (80132736)

Project Period (FY) 1997 – 1998
KeywordsBDNF / apoptosis / transcription / mitochondria / secretogranin II / PACAP / aconitase / calcium
Research Abstract

In this study, we investigated the mechanisms of attenuation of apoptosis of cerebellar granule cells (CGCs), which is controlled by Ca^<2+> influx into neurons, in terms of Ca^<2+> responsive gene expression and mitochondrial participation in apoptosis.
1. Survey for novel Ca^<2+> responsive genes (CaRGs) whose products are responsible for attenuating neuronal apoptosis.
Besides brain-derived neurotrophic factor (BDNF), we identified the secretogranin II and PACAP (pituitary adenylate cyclase polypeptide) genes whose expression can be controlled by Ca^<2+> suignals, and found that their processing, secretory products, secretoneurin and PACAP38, respectively, have the.attenuating effects on apoptosis of CGCs.
2. Establishment of DNA transfection for promoter analysis in primary neuronal cell culture.
Using calcium/phosphate-DNA precipitation method, we developed a convenient and reproducible conditions for DNA transfection in primary neuronal cell culture. Using this optimum condition, we have found that there could be multiple Ca^<2+> signaling pathways to control the expression of CaRGs in neurons.
3. Involvement of mitochondrial damage in Ca^<2+> deprivation-induced apoptosis of CGCs.
Upon a deprivation of Ca^<2+> influx into CGCs, inactivation of aconitase, a redox- sensitive TCA cycle enzyme, was induced with apoptosis. In a good correspondence to aconitase inactivation, the expression of manganese (Mn)-supcroxide dismutase gene decreased, indicating that a generation of superoxide radicals leads to mitochondrial damage. Upon recovery of Ca^<2+> influx, however, aconitase inactivation was attenuated in concert with attenuation of apoptosis.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Fujita, Y.: "Co-activation of secretogranin-II and BDNF genes mediated by calcium signals in mouse cerebellar granule cells." Mol.Brain Res.63. 316-324 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tabuchi, A.: "Inducibility of BDNF gene promoter I detected by calcium-phosphate mediated DNA transfection is confined to neuronal but not to glial cells." Biochem.Biophys.Res.Commun.253. 818-823 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ichikawa, D.: "Attenuation of cell death mediated by membrane depolarization different from that by exogenous BDNF in cultured cerebellar granule cells." Mol.Brain Res.56. 218-226 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Imaoka, T.: "In vivo gene transfer into the adult mammalian central nervous system by continuous injection of plasmid DNA-cationic liposome complex." Brain Res.780. 119-128 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 津田正明: "神経細胞におけるカルシウム応答遺伝子群" 生化学. (印刷中). (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 田渕明子: "カルシウム依存的な神経細胞死抑制に関わる遺伝子群の発現" 医学のあゆみ 別冊「神経細胞死制御」. 193-198 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kei Inaba, Junko Utsugi, Teruo Kuroda, Masaaki Tsuda and Tomofusa Tsuchiya: "Na+ (Li+) /H+ antiporter in Pseudomanas aeruginosa and effect of Li+ on cell growth." Biol.Pharm.Bull. 20. 621-624 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wakano Ogawa, T.Kayahara, M.Tsuda, T.Mizushima and T.Tsuchiya: "Isolation and characterization of an Esherichia coli mutant lacking the major serine transporter, and cloning of a serine transporter." J.Biochem.122. 1241-1246 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takashi Imaoka, Isao Date, Takashi Ohmoto, Tatsuji Yasuda and Masaaki Tsuda: "In vivo gene transfer into the adult mammalian central nervous system by continuous injection of plasmid DNA-cationic liposome complex." Brain Res.780. 119-128 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Daisuke ichikawa, Akiko Tabuchi, Akiko Taoka, Tomofusa Tsuchiya and Masaaki Tsuda: "Attenuation of cell death mediated by membrane depolarization different from that by exogenous BDNF in cultured cerebellar granule cells." Mol.Brain Res.56. 218-226 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Eiji Tamai, Tadashi Shimamoto, Masaaki Tsuda, Tohru Mizushima and Tomofusa Tsuchiya: "Conversion of temperature-sensitive to -resistant gene expression due to mutations in the promoter region of the melibiose operon in Esherichia coli." J.Biol.Chem.27. 16860-16864 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Junko Utsugi, kei Inaba, Teruo Kuroda, Masaaki Tsuda and Tomofusa Tsuchiya: "Cloning and sequencung of a novel Na+/H+ antiporter gene from Pseudomonas aeruginosa." Biochim.Biophysic.Acta.330-334 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akiko Tabuchi, Kuniaki Sano, Ryuuki Nakaoka, Chikako Nakatani and Masaaki Tsuda: "Inducibility of BDNF gene promoter I detected by calcium-phosphate mediated DNA transfection is confined to neuronal but not to glial cells." Biochem.Biophys.Res.Commun.253. 818-823 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasutaka Fujita, Jun Katagi, Akiko Tabuchi, Tomofusa Tsuchiya, and masaaki Tsuda: "Co-activation of secretogranin-II and BDNF genes mediated by calcium signals in mouse cerebellar granule cells." Mol.Brain Res.63. 316-324 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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