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Promotion of rescue of immortalized motor neuron-like cells by cytokines of interleukin-6 familiy.

Research Project

Project/Area Number 11672278
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionShowa Pharmaceutical University

Principal Investigator

UTSUNOMIYA Iku  Showa Pharmaceutical Universit, Department of Neuroscience, Assistant Professor, 薬学部, 講師 (70168722)

Co-Investigator(Kenkyū-buntansha) MIYATAKE Tadashi  Showa Pharmaceutical Universit, University, Department of Neuroscience, Professor, 薬学部, 教授 (50048998)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsNeurotrophic factor / Motor neuron / Acetylcholine receptor / Hybridoma / Gangliosides / CNTF / GM2 / IL-6 receptor
Research Abstract

To develop pharmacotherapy for motor neuron disease, we examined whether ciliary neurotrophic factor (CNTF) can alter serum-free cell survival of immortalized motor neuron-1ike cells, which were established by fusing mouse neuroblastoma N18TG2 with mouse motor neurons. One of the cell lines, NSC-34 exhibited cell survival in the presence of CNTF. NSC-34 preserves the most characteristics of motor neurons, such as the formation of neuromuscular junctions on co-cultured myotube. GM2 ganglioside is characteristic of motor neurons, and expressed highly in NSC-34. When NSC-34 was cultured with exogenous GM2 and CNTF, GM2 facilitated the cell survival effect of CNTF. In addition, GM2 synthase activity was enhanced up to 3.9-fold by culture in the presence of CNTF. Then we examined whether CNTF-induced cell survival is associated with the collaboration between GM2 and the CNTF receptor (CNTF-R). Despite the presence of CNTF (50 ng/ml), anti-CNTF-R antibody caused cell death and prevented the up-regulation of GM2 synthase expression. The addition of GM2 (1 to 20 μM) abrogated the anti-CNTF-R antibody effect which shortened cell survival and blocked GM2 synthase activation. Use of [<125>^I] CNTF showed the specificity of CNTF binding in NSC-34 cells in situ. GM2 produced a 5-fold increase in the CNTF binding affinity per cell but did not change the binding site number. The study by metabolic labeling with [1-<14>^C]N-acetyl-D-galactosamine ([<14>^C]GalNAc) showed that biosynthesized GM2 was involved in the immunoprecipitation of CNTF-R. These findings indicate that up-regulated GM2 synthesis induces functional conversion of CNTF-R to the activated state, in which it has high affinity for CNTF. We conclude that GM2 is a bio-regulating molecule of CNTF-R in motor neurons.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Usuki S.: "GM2 promotes ciliary neurotrophic factor-dependent rescue of immortalized motor neuron-like cells (NSC-34)"Neurochemical Research. 24. 281-286 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ren J.: "Localization of verotoxin receptors in nervous system"Brain Research. 825. 183-188 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 宇都宮 郁: "Vero毒素受容体の特性と神経系における局在"医学のあゆみ. 193. 742-743 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Usuki S.: "GM2 ganglioside regulates the function of ciliary neurotrophic factor receptor in murine immortalized motor neuron-like cells (NSC-34)"Neurochemical Research. 26. 375-382 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Utsunomiya I.: "Immunohistochemical detection of verotoxin receptors in nervous system"Brain Research Protocol. 8. 99-103 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Usuki S., Cashman N. R., Miyatake T.: "GM2 promotes ciliary neurotrophic factor-depandent rescue of immortalised motor neuron-like cell(NSC-34)"Brain Res. 825(1-2). 183-188 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ren J., Utsunomiya I., Taguchi K., Ariga T., Tai T., Ihara Y., Miyatake T.: "Localization of verotoxin receptors in nervous system."Neurochem. Res. 24(2). 281-286 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Utsunomiya I., Miyatake T: "Characterization of verotoxin receptors and its localization in nervous system."J. Clin. Med. 193(3). 742-743 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Usuki S., Ren J., UtsunomiyaI., Cashman N. R., Inokuchi J., Miyatake T.: "GM2 ganglioside regulates the function of ciliary neurotrophic factor receptor in murine immortalized motor neuron-like cells (NSC-34)."Neurodhem. 26(4). 375-382 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Utsunomiya I, Ren J, Taguchi K, Ariga T, Tai T, Ihara Y, Miyatake T.: "Immunohistochemical detection of verotoxin receptors in nervous system."Brain ResProtoc. 8(2). 99-103 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Usuki S.: "GM2 ganglioside regulates the function of ciliary neurotrophic factor receptor in murine immortalized motor neuron-like cells (NSC-34)"Neurochemical Research. 26・4. 375-382 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Utsunomiya I.: "Immunohistochemical detection of verotoxin receptors in nervous system"Brain Research Protocol. 8・2. 99-103 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 宇都宮郁: "Vero毒素受容体の特性と神経系における局在"医学のあゆみ. 193・9. 742-743 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Usuki S.: "GM2 ganglioside regulates the function of ciliary neurotrophic factor receptor in murine immortalized motor neuron-like cells (NSC-34)"Neurochemical Research. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Usuki S.: "GM2 promotes ciliary neurotrophic factor-dependent rescue of immortaliized motor neuron-like cell (NSC-34)"Neurochemical Research. 24・2. 281-286 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ren J.: "Localization of verotoxin receptors in nervous system"Brain Research. 825・1〜2. 183-188 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 宇都宮 郁: "Vero毒素受容体の特性と神経系における局在"医学のあゆみ. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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