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Generation of Cultured Cell Lines to Study Alzheimer's Disease

Research Project

Project/Area Number 07557165
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 医薬分子機能学
Research InstitutionThe University of Tokushima

Principal Investigator

YAMAUTI Takasi  Faculty of Pharm.sci., The University of Tokushima Professor, 薬学部, 教授 (90041813)

Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥19,200,000 (Direct Cost: ¥19,200,000)
Fiscal Year 1997: ¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1996: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1995: ¥6,900,000 (Direct Cost: ¥6,900,000)
KeywordsAl_3 heimer's disese / Ca^<2+> / calmoclulin / tau protcin / phophorylition / protein kinase / clmed cell line / タウタンパク質 / アミロイドプレローサータンパク / アルツハイマー / タウ / 培養細胞 / 遺伝子導入 / 神経分化
Research Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide, causing progressive dementia and death in many millions of people. Neurofibrillary tangles are characteristic lesions found in the brain of AD.These tangles are composed of paired helical filaments (PHFs), and the major component is the microtubule-associated protein tau. PHF-tau is abnormally hyperphosphorylated in AD.In order to investigate the control of phosphorylation of tau protein, we studied in cultured cells and obtained some interesting results as follows ; (i) We constructed the expression vector of tau protein and protein kinases, and transfected them to neuroblastoma cells or embryonic carcinoma cells (cell line P-19). Cloned cells expressing tau protein or protein kinases were generated and isolated. (ii) Treatment of retinoic acid on P-19 cells increased the expression of CaM kinase II and induced to change the splicing pattern of the delta isoform of the kinase. (iii) Neurite outgrowth was stimulated in cells overexpressing CaM kinase II with protein kinase C inhibitors, indicating that differentiation and proliferation of neural cells were regulated by the activity of protein kinase C and CaM kinase II.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Teyashima, T.et al.: "Alpha calcium/calmidiulin-dependent..." Anat.Embryol.192. 123-136 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ogawara, M.et al.: "Differential targeting of protein kinase c..." J.Cell Biol.131. 1055-1066 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshimura, Y.et al.: "Purification and charcterization S6 active..." J.Biochem.119. 268-273 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nishioka, N. et al.: "Gene of rat Ca^<2+>/Calmodulin-dependent..." FEBS Lett. 396. 333-336 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nomura, T. et al.: "Overexpression of α and β isoforms of ..." Brain Res.766. 129-141 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshimura, Y.et al.: "Phosphorylation-dependent reversible..." J.Biol.Chem.272. 26354-26359 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Terashima, T., Ochiishi, T., and Yamauchi, T.: "Alpha calcium/calmodulin-dependent protein kinse II immunoreactivity in corticospinal neurons : combination of axonal transport method and immunofluorescence." Anat.Embryol.192. 123-136 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ogawara, M., Inagaki, N., Tsujimura, K., Takai, Y., Sekimata, M., Ha, M.H., Imajoh-Ohmi, S., Hirai, S., Ohno, S., Sugiura, H., Yamauchi, T., and Inagaki, M.: "Differential targeting of protein kinase C and CaM kinase II signalings to vimentin." J.Cell Biol.131. 1055-1066 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshimura, Y., Nomura, T., and Yamauchi, T.: "Purification and characterization of active fragment of Ca^<2+>/calmodulin-dependent protein kinase II from the post-synaptic density in the rat fore brain." J.Biochem.119. 268-273 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nishioka, N., Shiojiri, M., Kadota, S., Morinaga, H., Kuwahara, J., Arakawa, T., Yamamoto, S., and Yamauchi, T.: "Gene of rat Ca^<2+>/calmodulin-dependent protein kinase II alpha isoform -its cloning and whole structure." FEBS Lett.396. 333-336 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nomura, T., Kumatoriya, K., Yoshimura, Y., and Yamauchi, T.: "Overexpression of alpha and beta isoforms of Ca^<2+>/camodulin-dependent protein kinase II in neuroblastoma cells - H-7 promotes neurite outgrowth." Brain Res.766. 129-141 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshimura, Y., and Yamauchi, T.: "Phosphorylation-dependent reversible association of Ca^<2+>/calmodulin-dependent protein kinase II with the postsynaptic densities." J.Biol.Chem.272. 26354-26359 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nomura,T.et al: "overexpression of α and β isoforms of Ca^<2+>/calmodulin-dependent protein kinase II ・・・・" Brain Res.766. 129-141 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshimura,Y.et al: "phosphorylation-dependent reversible association of Ca^<2+>/calmodulin ・・・・" J.Biol.Chem.272. 26354-26359 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujii,M.et al: "generation of immortalized murine forebrain cell lines expressing α ・・・・" Biol.Pharm.Bull. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamauchi,T.et al: "phosphorylation-dependent reversible translocation of ・・・・" Life Sci. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshimura,Y.,et al.: "Purification and characterization of active fragment of Ca^<2+>/calmodulin-dependent protein kinase II from the post-synaptic density in the rat forebrain" J.Biochem.119. 268-273 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nishioka,N.,et al.: "Gene of rat Ca^<2+>/calmodulin-dependent protein kinase II α isoform-its cloning and whole structure" FEBS Lett.396. 333-336 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Terashima,T.et al: "Aepha calcium/Calmodulin-dependent protein kinaceII…" Arat,Embryal.192. 123-136 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamaushi,T.et al: "Investigetin and developmental chonpes in protein…" Nevroscience protcols. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshimura,Y.et al: "Purificatin and Chovacterizatin of active frapment of Ca^<2+>…" J.Biochem.(in press). (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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