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Emerging pathophysiological roles of ganglioside GM3

Research Project

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
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2012: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2011: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
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 / スフィンゴ糖脂質 / メタボリックシンドローム / マクロファージ / 内臓脂肪 / インスリン抵抗性 / 慢性炎症 / 視床下部 / 過食 / KKAyマウス / T細胞 / アレルギー / 喘息
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=.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (67 results)

All 2014 2013 2012 2011 Other

All Journal Article (17 results) (of which Peer Reviewed: 11 results,  Open Access: 1 results) Presentation (41 results) (of which Invited: 10 results) Book (4 results) Remarks (3 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

    • Related Report
      2013 Final Research Report
  • [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

    • Related Report
      2013 Final Research Report
  • [Journal Article] Functional mapping and implications of substrate specificity of the yeast high-affinity leucine permease Bap22014

    • Author(s)
      上村 聡志,井ノ口 仁一 他
    • Journal Title

      Biochimica et Biophysica Acta

      Volume: 1838 Issue: 7 Pages: 1719-1729

    • DOI

      10.1016/j.bbamem.2014.03.018

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [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

    • Related Report
      2013 Final Research Report
  • [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

      Volume: 31 Issue: 2 Pages: 101-108

    • DOI

      10.1007/s10719-013-9499-1

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Heterogeneity of gangliosides among T cell subsets2013

    • Author(s)
      Jin-ichi Inokuchi
    • Journal Title

      Cell Mol Life Sci

      Volume: 70 Issue: 17 Pages: 2000-2008

    • DOI

      10.1007/s00018-012-1208-x

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Physiological Significance of Ganglioside Species Selectively Expressed on Individual T Cell Subsets2013

    • Author(s)
      永福 正和,井ノ口 仁一
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 25 Issue: 144 Pages: 159-169

    • DOI

      10.4052/tigg.25.159

    • NAID

      130004841373

    • ISSN
      0915-7352, 1883-2113
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [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

    • Related Report
      2013 Final Research Report
  • [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

    • Related Report
      2013 Final Research Report
  • [Journal Article] Impairment of hippocampal long-term potentiation and failure of learning in mice treated with D-threo-1-phenyldecanoylamino-1-propanol.2012

    • Author(s)
      Hiroki Fujiwara
    • Journal Title

      Biomedical Res.

      Volume: 33 Pages: 265-271

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD4+T細胞とCD8+T細胞の活性化におけるラフトガングリオシドの相違2012

    • Author(s)
      Masakazu Nagafuku
    • Journal Title

      東北薬科大学研究誌

      Volume: 59 Pages: 35-43

    • NAID

      40018833141

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [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, Inokuchi J
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 109 Issue: 6

    • DOI

      10.1073/pnas.1114965109

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dissociation of the insulin receptor from caveolae during TNFα-induced insulin2012

    • Author(s)
      関本淳二、井ノ口仁一, 他
    • Journal Title

      FEBS Letters

      Volume: 586 Pages: 191-195

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [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

    • Related Report
      2013 Final Research Report
  • [Journal Article] Physiopathological function of hematoside (GM3 ganglioside)2011

    • Author(s)
      井ノ口仁一
    • Journal Title

      Proceedings of the Japan Academy, Series B

      Volume: 87 Issue: 4 Pages: 179-198

    • DOI

      10.2183/pjab.87.179

    • NAID

      130000668836

    • ISSN
      0386-2208, 1349-2896
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 聴覚機能における複合糖脂質の役割2011

    • Author(s)
      郷慎司、吉川弥里、井ノ口仁一
    • Journal Title

      生化学

      Volume: 83 Pages: 179-188

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glycoconjugates in the mammalian sauditory system2011

    • Author(s)
      郷慎司、吉川弥里、井ノ口仁一
    • Journal Title

      J Neurochem

      Volume: 116(5) Issue: 5 Pages: 756-763

    • DOI

      10.1111/j.1471-4159.2010.07099.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [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
    • Related Report
      2013 Final Research Report
  • [Presentation] GM3 and Diabetes2014

    • Author(s)
      Inokuchi J
    • Organizer
      Gordon Research Conference on Glycolipis and Sphingolipid
    • Place of Presentation
      Ventura, CA, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] GM3 and Diabetes.2014

    • Author(s)
      井ノ口 仁一
    • Organizer
      Gordon Research Conference on Glycolipis and Sphingolipid
    • Place of Presentation
      Ventura, CA, USA
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] T細胞の分化制御および免疫疾患におけるスフィンゴ糖脂質の発現の意義2014

    • Author(s)
      井ノ口 仁一
    • Organizer
      難治疾患共同研究拠点集会「糖鎖免疫 Glyco-Immunology 2014」
    • Place of Presentation
      東京医科歯科大学
    • Related Report
      2013 Annual Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [Presentation] CD4 and CD8T cells require different gangliosides for activation.2013

    • Author(s)
      井ノ口 仁一
    • Organizer
      The 54nd International Conference on Bioscience of Lipids
    • Place of Presentation
      Bari, Italy
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 炎症性シグナルメディエーターとしてのガングリオシドの脂肪組織、視床下部および免疫疾患における病態生理学的意義2013

    • Author(s)
      井ノ口 仁一
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 生体恒常性の破綻とスフィンゴ糖脂質代謝2013

    • Author(s)
      井ノ口 仁一
    • Organizer
      第11回日本糖質科学コンソーシアムシンポジウム
    • Place of Presentation
      東北薬科大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] 聴覚におけるガングリオシドの役割2013

    • Author(s)
      井ノ口 仁一
    • Organizer
      第55回日本脂質生化学会
    • Place of Presentation
      松島
    • Related Report
      2013 Annual Research Report
  • [Presentation] マクロファージは内臓脂肪細胞のガングリオシド発現量を支配し、脂肪細胞の分化成熟とインスリン抵抗性を制御している(Macrophages govern spatiotemporal expression of gangliosides in adipocytes for regulation of adipogenesis and insulin signaling)2013

    • Author(s)
      井ノ口 仁一
    • Organizer
      第32回日本糖質学会年会
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
  • [Presentation] GM3合成酵素欠損マウスの聴覚障害発症機序(Elucidation on the mechanism of hearing loss in ganglioside GM3 synthase deficient mice)2013

    • Author(s)
      井ノ口 仁一
    • Organizer
      第7回東北糖鎖研究会
    • Place of Presentation
      新潟
    • Related Report
      2013 Annual Research Report
  • [Presentation] 筋分化過程におけるスフィンゴ糖脂質発現変化とその意義(Distinct alteration on the expression of glycosphingolipids during myotube differentiation and its significance)2013

    • Author(s)
      新井 詩織
    • Organizer
      第7回東北糖鎖研究会
    • Place of Presentation
      新潟
    • Related Report
      2013 Annual Research Report
  • [Presentation] T細胞の分化成熟におけるスフィンゴ脂質の発現と機能的役割 (Expression pattern of sphingolipids and its role in T cell development)2013

    • Author(s)
      豊島 かおる
    • Organizer
      第7回東北糖鎖研究会
    • Place of Presentation
      新潟
    • Related Report
      2013 Annual Research Report
  • [Presentation] Distict expression profile of sphingolipid species during T cell development.2013

    • Author(s)
      井ノ口 仁一
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      千葉
    • Related Report
      2013 Annual Research Report
  • [Presentation] Lipids in Metabolic Syndrome2013

    • Author(s)
      井ノ口仁一
    • Organizer
      Ely-T lab workshop
    • Place of Presentation
      宮城
    • Related Report
      2012 Annual Research Report
  • [Presentation] CD4 and CD8T cells require different gangliosides for activation2013

    • Author(s)
      井ノ口仁一
    • Organizer
      The 14th International Membrane Research Forum
    • Place of Presentation
      京都
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] The role of GM3 in biological membranes2012

    • Author(s)
      井ノ口仁一
    • Organizer
      Ely-T lab workshop
    • Place of Presentation
      フランス
    • Year and Date
      2012-03-12
    • Related Report
      2011 Annual Research Report
  • [Presentation] Ganglioside GM3 participates in the pathogenesis of metabolic syndrome2012

    • Author(s)
      井ノ口仁一
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      イタリア
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] ガングリオシドによるT細胞サブセット特異的免疫制御2012

    • Author(s)
      井ノ口仁一
    • Organizer
      第54回日本脂質生化学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] スフィンゴ脂質によるT細胞サブセットの特異的免疫制御2012

    • Author(s)
      井ノ口仁一
    • Organizer
      スフィンゴテラピィ研究会
    • Place of Presentation
      金沢
    • Related Report
      2012 Annual Research Report
  • [Presentation] GM3 synthase depletion ameliorates glucose tolerance in obesity related type 2 diabetes mice2012

    • Author(s)
      今津進
    • Organizer
      第72回アメリカ糖尿病学会
    • Place of Presentation
      アメリカ
    • Related Report
      2012 Annual Research Report
  • [Presentation] Ganglioside-dependent membrane microdomain: involvement of insulin resistance and T cell immunity2012

    • Author(s)
      井ノ口仁一
    • Organizer
      SialoGlyco2012
    • Place of Presentation
      台北
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] GM3合成酵素欠損糖尿病モデルマウスでは体重増加が抑制されインスリン感受性が亢進している2012

    • Author(s)
      今津進
    • Organizer
      日本肥満学会
    • Place of Presentation
      京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] A minimal influence of glycosylation of ganglioside on th in vivo Th 1-dominant responses in mouse2012

    • Author(s)
      Keiko Udaka
    • Organizer
      代41回日本免疫学会
    • Place of Presentation
      神戸
    • Related Report
      2012 Annual Research Report
  • [Presentation] T細胞サブセットの機能的レパトア選択におけるガングリオシド分子種の役割2012

    • Author(s)
      井ノ口仁一
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] T cell immunity and gangliosides2011

    • Author(s)
      井ノ口仁一
    • Organizer
      The annual meeting of consortium of functional glycobiology
    • Place of Presentation
      シアトル
    • Year and Date
      2011-11-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] Involvement of membrane microdomains in the pathogenesis of metabolic syndrome and allergic inflammation2011

    • Author(s)
      井ノ口仁一
    • Organizer
      糖鎖科学日欄Joint Seminar
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] Membrane microdomain ortho-signaling therapy2011

    • Author(s)
      井ノ口仁一
    • Organizer
      The 31^<st> Naito Conference on Glycan Expression and Regulation [II]
    • Place of Presentation
      札幌
    • Year and Date
      2011-09-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Involvement of membrane microdomains in the pathogenesis metabolic syndrome and asthma2011

    • Author(s)
      井ノ口仁一
    • Organizer
      52^<nd> International Conference on the Bioscience of Lipids
    • Place of Presentation
      ワルシャワ
    • Year and Date
      2011-09-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] Physiopathological function of GM3 ganglioside2011

    • Author(s)
      井ノ口仁一
    • Organizer
      GLYCO21
    • Place of Presentation
      ウィーン
    • Year and Date
      2011-08-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] GM3 ganglioside participates in the pathogenesis of metabolic syndrome and allergic asthma2011

    • Author(s)
      井ノ口仁一
    • Organizer
      Second Joint Austria/Japan Seminar
    • Place of Presentation
      ウィーン
    • Year and Date
      2011-08-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] T細胞免疫におけるガングリオシド発現の意義

    • Author(s)
      永福正和
    • Organizer
      第78回日本生化学会東北支部例会
    • Place of Presentation
      山形
    • Related Report
      2012 Annual Research Report
  • [Presentation] 糖代謝とスフィンゴ糖脂質

    • Author(s)
      郷慎司
    • Organizer
      第78回日本生化学会東北支部例会
    • Place of Presentation
      山形
    • Related Report
      2012 Annual Research Report
  • [Presentation] O-GlcNAc修飾を介したスフィンゴ糖脂質代謝制御機構

    • Author(s)
      郷慎司
    • Organizer
      日本糖質学会
    • Place of Presentation
      鹿児島
    • Related Report
      2012 Annual Research Report
  • [Presentation] メタボリックシンドロームおよびアレルギー疾患におけるGM3ガングリオシドの病態生理学的意義

    • Author(s)
      井ノ口仁一
    • Organizer
      FCCAグライコサイエンス若手フォーラム2012
    • Place of Presentation
      鹿児島
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] O-GlcNAc修飾を介したスフィンゴ糖脂質代謝制御機構

    • Author(s)
      郷慎司
    • Organizer
      東北糖鎖研究会
    • Place of Presentation
      弘前
    • Related Report
      2012 Annual Research Report
  • [Presentation] スフィンゴ糖脂質代謝と生活習慣病

    • Author(s)
      井ノ口仁一
    • Organizer
      平成24年度東北薬科大学分子生体膜研究所戦略的研究基盤形成支援事業シンポジウム
    • Place of Presentation
      宮城
    • Related Report
      2012 Annual Research Report
  • [Presentation] ガングリオシドのラフトにおける機能発現機構と病態生理学的意義

    • Author(s)
      井ノ口仁一
    • Organizer
      平成24年度日本薬学会北海道支部例会
    • Place of Presentation
      札幌
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 肥満・慢性炎症関連病態とガングリオシド GM3

    • Author(s)
      井ノ口仁一
    • Organizer
      平成24年度日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] O-GlcNAc修飾を介したスフィンゴ糖脂質代謝制御機構

    • Author(s)
      郷慎司
    • Organizer
      平成24年度日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Book] Handbook of Glycosyltransferases and Related Genes 2nd ed2014

    • Author(s)
      上村 聡志,井ノ口 仁一
    • Total Pages
      1707
    • Publisher
      Springer Japan
    • Related Report
      2013 Annual Research Report
  • [Book] Inhibition of ganglioside biosynthesis as a novel therapeutic approach in insulin resistance. Handbook of Experimental Pharmacology 2032013

    • Author(s)
      Inokuchi J
    • Publisher
      Springer
    • Related Report
      2013 Final Research Report
  • [Book] 第三の生命鎖 糖鎖の機能と疾患2013

    • Author(s)
      井ノ口 仁一
    • Total Pages
      225
    • Publisher
      羊土社
    • Related Report
      2013 Annual Research Report
  • [Book] Handbook of Experimental Pharmacology2011

    • Author(s)
      井ノ口仁一
    • Total Pages
      13
    • Publisher
      Springer
    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2013 Final Research Report
  • [Remarks] 東北薬科大学分子生体膜研究所機能病態分子学教室

    • URL

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

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2011 Annual Research Report
  • [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
    • Related Report
      2013 Final Research Report
    • 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
    • Related Report
      2013 Final Research Report
    • Overseas

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Published: 2011-04-06   Modified: 2019-07-29  

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