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2013 Fiscal Year Final Research Report

Emerging pathophysiological roles of ganglioside GM3

Research Project

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Project/Area Number 23370064
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionTohoku Pharmaceutical University

Principal Investigator

INOKUCHI Jin-ichi  東北薬科大学, 薬学部, 教授 (70131810)

Co-Investigator(Renkei-kenkyūsha) UEMURA Satoshi  青山学院大学, 理工学部, 助教 (10399975)
NAGAFUKU Masakazu  東北薬科大学, 薬学部, 助教 (20399976)
GO Shinji  東北薬科大学, 薬学部, 助教 (10458218)
Project Period (FY) 2011-04-01 – 2014-03-31
Keywordsスフィンゴ等脂質 / ガングリオシド / 免疫シナプス / ラフト / CD4+ T細胞 / CD8+ T細胞 / アレルギー治療 / 喘息治療
Research Abstract

We have found that CD8T cells express very high levels of o-series gangliosides, but on the other hand, CD4T cells preferably express a-series gangliosides. In the TCR dependent activation, CD4T cells selectively require a-series gangliosides, but CD8T cells do require only o-series gangliosides but not a-series gangliosides. Ganglioside GM3 synthase-deficient mice lacking a-series gangliosides neither exhibited the TCR-dependent activation of CD4T nor developed ovalbumin-induced allergic airway inflammation. These findings imply that the distinct expression pattern of ganglioside species in CD4T and CD8T cells define the immune function of each T cell subset.
We also propose a working hypothesis =metabolic disorders, such as type2 diabetes, are membrane microdomain disorders caused by aberrant expression of gangliosides=.

  • Research Products

    (15 results)

All 2014 2013 2012 2011 Other

All Journal Article (7 results) Presentation (4 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Journal Article] GM3 and Diabetes2014

    • Author(s)
      Inokuchi J
    • Journal Title

      Glycoconj. J

      Volume: 31 Pages: 193-197

  • [Journal Article] Loss of hydroxyl groups from the ceramide moiety can modify the lateral diffusion of membrane proteins in Saccharomyces cerevisiae2014

    • Author(s)
      Uemura S., Shisido F., Tani M., Mochizuki T., Abe T. and Inokuchi J
    • Journal Title

      J. Lipid Res

  • [Journal Article] Heterogeneity of gangliosides among T cell subsets2013

    • Author(s)
      Inokuchi J, Nagafuku M, Ohno I. and Suzuki A.
    • Journal Title

      Cell. Mol. Life Sci

      Volume: 70 Pages: 3067-75

  • [Journal Article] Expression machinery of GM4 : the excess amounts of GM3/GM4S synthase (ST3GAL5) are necessary for GM4 synthesis in mammalian cells2013

    • Author(s)
      Uemura S, Go S, Shishido F, Inokuchi J
    • Journal Title

      Glycoconj. J

    • DOI

      10.1007/s10719-013-9499-1

  • [Journal Article] CD4 and CD8 T cells require different membrane gangliosides for activation2012

    • Author(s)
      Nagafuku M, Okuyama K., Onimaru Y., Suzuki A., Odagiri Y., Yamashita T., Iwasaki K., Fujiwara M., Takayanagi M., Ohno I. and Inokuchi J
    • Journal Title

      Proc. Natl. Acad. Sci.USA

      Volume: 109 Pages: E336-E342

  • [Journal Article] Dissociation of the insulin receptor from caveolae during TNF α-induced insulin resistance and its recovery by D-PDMP2012

    • Author(s)
      Sekimoto J., Kabayama K., Gohara K., and Inokuchi J
    • Journal Title

      FEBS Lett

      Volume: 586 Pages: 191-195

  • [Journal Article] Physiopathological function of hematoside (GM3 ganglioside)2011

    • Author(s)
      Inokuchi, J
    • Journal Title

      Proc. Jpn. Acad., Ser. B

      Volume: 87 Pages: 179-198

  • [Presentation] CD4 and CD8T cells require different gangliosides for activation2014

    • Author(s)
      Inokuchi J
    • Organizer
      The 52nd International Conference on Bioscience of Lipids
    • Place of Presentation
      Bari, Italy
    • Year and Date
      20140917-22
  • [Presentation] GM3 and Diabetes2014

    • Author(s)
      Inokuchi J
    • Organizer
      Gordon Research Conference on Glycolipis and Sphingolipid
    • Place of Presentation
      Ventura, CA, USA
    • Year and Date
      20140112-17
  • [Presentation] CD4 and CD8T cells require different gangliosides for activation2013

    • Author(s)
      Inokuchi J
    • Organizer
      The 14th International Membrane Research Forum
    • Place of Presentation
      Kyoto
    • Year and Date
      20130315-17
  • [Presentation] Ganglioside-dependent membrane microdomain : Involvement of insulin resistance, hearing function and T cell immunity2013

    • Author(s)
      Inokuchi J
    • Organizer
      GlycoMedicine Seminar
    • Place of Presentation
      Academia Sinica Taipei
    • Year and Date
      2013-12-08
  • [Book] Inhibition of ganglioside biosynthesis as a novel therapeutic approach in insulin resistance. Handbook of Experimental Pharmacology 2032013

    • Author(s)
      Inokuchi J
    • Total Pages
      165-78
    • Publisher
      Springer
  • [Remarks]

    • URL

      http://www.tohoku-pharm.ac.jp/homepages/kinoubyoutai/TOP.html

  • [Patent(Industrial Property Rights)] 高脂血症治療剤のスクリーニング方法

    • Inventor(s)
      井ノ口仁一, 永福正和,㏿水博孝
    • Industrial Property Rights Holder
      JST
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      特許第5077901号
    • Overseas
  • [Patent(Industrial Property Rights)] ヘルパーT細胞の選択的機能制御法

    • Inventor(s)
      井ノ口仁一, 永福正和, 大野勳, 奥山香織
    • Industrial Property Rights Holder
      JST
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      特許第5232241号
    • Overseas

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Published: 2015-06-25  

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