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Studies on the significance of bioactive gangliosides in cellular growth and differntiation.

Research Project

Project/Area Number 60440102
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field 物質生物化学
Research InstitutionFaculty of Medicine, Unversity of Tokyo

Principal Investigator

NAGAI Yoshitaka  Faculty of Medicine, University of Tokyo; Professor, 医学部, 教授 (80072974)

Co-Investigator(Kenkyū-buntansha) OSANAI Taka  Faculty of Medicine, University of Tokyo; Technical official, 医学部, 技官(教務) (60126018)
TSUJI Shuichi  Faculty of Medicine, University of Tokyo; Research associate, 医学部, 助手 (90124677)
SANAI Yutaka  Faculty of Medicine, University of Tokyo; Research associate, 医学部, 助手 (40150289)
IWAMORI Masao  Faculty of Medicine, University of Tokyo; Associate Prof., 医学部, 助教授 (90110022)
Project Period (FY) 1985 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥24,200,000 (Direct Cost: ¥24,200,000)
Fiscal Year 1988: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1987: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1986: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1985: ¥17,000,000 (Direct Cost: ¥17,000,000)
KeywordsGangliosides / Protein phosphorylation / Neuroblastoma / Signal transduction / Inter-cellular signal transduction / MDCK / 3Y1 / ドーム形成 / Neuro2a / 細胞表層 / タンパクリン酸化酵素 / ガン遺伝子 / 遺伝子導入 / 神経突起伸展作用 / 腎細胞株
Research Abstract

Carbohydrate recognition at cell surface is known to importantly be involved in cell to cell interactions, cell growth and differentiation.Most of such modulatory potentials have so far been reported on a family of sialylated glycosphingolipids, gangliosides, using cultured cell system added with these glycolipids exogenously. We previously reported that a disialoganglioside GD3 strongly promotes ions and water transport in cultured kidney epithelial cells (MDCK). Newly and specific appearance of GD3 was observed in rat embryonic fibroblastic cells, 3Y1, which were transfected and transformed with various oncogenes of DNA-virus origin (adenovirus E1A, SV40-T and myc). The monoclonal antibody to GD3 reversibly inhibits cell growth of these cells. The remarkable elevation of GD3 was reported on neuron and glial cells in their proliferative states. More recently we have found that a tetrasialoganglioside G 1b specifically can promote differentiation of the human neuroblastoma cells, leading to the promotion of neuritogenesis and also that G 1b specifically stimulates the phosphorylation of several cell surface proteins of the same cells, when the G 1b and ATP are added to the cells. The results indicate that this cell surface protein phosphorylation might be carried out by unique cell surface membrane protein kinase(s) (ecto-Gg kinase) which is specifically activated by a particular ganglioside. Inhibition of this phosphorylation resulted in the inhibition of G 1b-dependent promotion of neuritogenesis, strongly suggesting the interrelationship between those two cell events and occurrence of a new biosignal transduction, ecto biosignal transduction system.

Report

(4 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1986 Annual Research Report
  • 1985 Annual Research Report
  • Research Products

    (48 results)

All Other

All Publications (48 results)

  • [Publications] S.Tsuji: J.Biochem.97. 969-972 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T.Shimada: Thrombosis Res.38. 21-31 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] M.Iwamori: J.Biochem.98. 1561-1569 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] J.Nakajima: Biochim.Biophys.Acta. 876. 65-71 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] M.Iwamori: Am.Chem.Soc.25. 889-896 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] S.Kosugi: Biochem.Biophys.Res.Commun.143. 848-855 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] N.Rodrig: FEBS Lett.221. 315-319 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T.Chiba: Biochim.Biophys.Acta.930. 10-18 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] H.Nakaishi: Biochem.Biophys.Res.Commun.150. 760-765 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] H.Nakaishi: Biochem.Biophys.Res.Commun.150. 766-774 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] S.Tsuji: J.Neurochem.50. 415-423 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] N.Rodrig: J.Biochem.104. 215-219 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] S.Tsuji: J.Biochem.104. 498-503 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] H.Nakaishi: Gancer Res.48. 59-66 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Y.Nagai: "Bioactive gangliosides:A new type of biologically active cell membrane compounds.in"Natural products and biological activities"" University of Tokyo Press, 153-165 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Y.Nagai: "Functional analysis of ganglioside-respondable human neuroblastoma cell lines.in"Gangliosides and neuronal plasticity"" Liviana Press,Padova, 231-244 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Y.Nagai: "Gangliosides in recognitive cell interaction and carbohydrate-mediated biosignalling.in"Lectins and glycoconjugates in oncology."" Springer-Verlag.Berlin, 59-66 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Y.Nagai: "Cell biological significance of gangliosides in neural differentiation and development:critique and proposals.in"New trends in gangliosides research:neurochemical and neuroregener" Liviana Press,Padova, 329-350 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] S.Tsuji: "Bioactive gangliosides. IV. ganglioside GQlb/Ca^<2+> dependent protein kinase activity exists in the plasma membrane fraction of neuroblastoma cell line, GOTO." J. Biochem.97. 969-972 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T.Shimada: "Activation of factor XII and prekallikrein with cholesterol sulfate." Thrombosis Res.38. 21-31 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] M.Iwamori: "Rabbit thymus gangliosides: species-and organ-specific distribution, age-dependence and their cell biological significance." J. Biochem.98. 1561-1569 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] J.Nakajima: "Bioactive gangliosides: analysis of functional structures of the tetrasialoganglioside GQlb which promotes neurite outgrowth." Biochim. Biophys. Acta. 876. 65-71 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] M.Iwamori: "Gangliosides as markers of cortisone-sensitive and cortisone-resistant rabbit thymocytes: characterization of thymus-specific gangliosides and preferential changes of particular gangliosides in the thymus of cortisone-treated rabbits." Am. Chem. Soc.25. 889-896 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] S.Kosugi: "Biological effect of anti-fucosyl GM1 ganglioside antibody on cyclic adenosine 3',5'-monophosphate production in Frt15 rat thyroid cells." Biochem. Biophys. Res. Commun.143. 848-855 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] N.Rodrig: "Gangliosides stimulate dome formation in cultured canine kidney epithelial cell line (MDCK)." FEBS Lett.221. 315-319 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T.Chiba: "Cerebroside sulfuric ester (sulfatide) induces oxygen radical generation in guinea-pig leukocytes." Biochim. Biophys. Acta. 930. 10-18 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] H.Nakaishi: "Analysis of cellular expression of gangliosides by gene transfection I: GD3 expression in myc-transfected and transformed 3Y1 correlates anchorage-independent growth activity." Biochem. Biophys. Res. Commun.150. 760-765 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] H.Nakaishi: "Analysis of cellular expression of gangliosides by gene transfection II: rat 3Y1 cells transformed with several DNAs containing oncogenes (fes, fps, ras and src) invariably express sialosylparagroboside." Biochem. Biophys. Res. Commun.150. 766-774 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] S.Tsuji: "Synthetic sialyl compounds as well as natural gangliosides induce neuritogenesis in a mouse neuroblastoma cell line (Neuro2a)." J. Neurochem.50. 415-423 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] N.Rodrig: "Uncoupling of intracellular cyclic AMP and dome formation in cultured canine kidney epithelial cells: effect of gangliosides and vasopressin." J. Biochem.104. 215-219 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] S.Tsuji: "A novel, carbohydrate signal-mediated cell surface protein phosphorylation: ganglioside GQlb stimulates ecto-protein kinase activity on the cell surface in a human neuroblastoma cell line, GOTO." J. Biochem.104. 498-503 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] H.Nakaishi: "Neosynteses of neolacto- and novel ganglio-series gangliosides in a rat fibroblastic cell line brought about by transfection with the v-fes oncogene-containing gardnerarnstein strain feline sarcoma virus DNA." Cancer. Res.48. 1753-1758 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Y.Nagai: Bioactive gangliosides: A new type of biologically active cell membrane compounds. in "Natural products and biological activities". University of Tokyo Press, 153-165 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Y.Nagai: Functional analysis of ganglioside-respondable human neuroblastoma cell lines. in "Gangliosides and neuronal plasticity" Eds. by G.Tettamanti et al.Liviana Press, Padova, 231-244 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Y.Nagai: Gangliosides in recognitive cell interaction and carbohydrate-mediated biosignalling. in "Lectins and glycoconjugates in oncology" Eds. by H.J.Gabius and G.A.Nagel. Springer-Verlag, Berlin., 59-66 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Y.Nagai: Cell biological significance of gangliosides in neural differentiation and development: critique and proposals. in "New trends in gangliosides research: neurochemical and neurogenerative aspects." Eds. by R.W. Ledeen et al.Liviana Press, Padova, 329-350 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Rodrig,N.: FEBS Lett.221. 315-319 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] Tsuji,S.: J.Neurochem.50. (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Ledeen,R.W;et al.eds,Nagai,Y.: "New trends in Ganglioside Research;Neurochemical and Neurorogenerative Aspects." Liviana Press,Padova, (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Nagel,G.A.;et al.eds,Nagai,Y.: "Lectin and Glycoconjugate in oncology." Springer-Verlag,Heidelberg, (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] J.NAKAJIMA: Biochem.Biophys.Acta.876. 65-71 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Y.NAGAI: Chemistry and Physics of Lipids. 42. 91-103 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Y.NAGAI(Eds.by H.IMURA et al): ""Natural Products and Biological Activities."(Bioactive gangliosides: A new type of biologically active cell membrane compounds.)" University of Tokyo Press, 5)371(153-16 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] J.Biochem.97. (1985)

    • Related Report
      1985 Annual Research Report
  • [Publications] Glycoconjugates(8th Proc.Int.Symp.). 2. (1985)

    • Related Report
      1985 Annual Research Report
  • [Publications] J.Biochem.98. (1985)

    • Related Report
      1985 Annual Research Report
  • [Publications] Exp.Hematol.13. (1985)

    • Related Report
      1985 Annual Research Report
  • [Publications] INSERM. 126. (1984)

    • Related Report
      1985 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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