2013 Fiscal Year Final Research Report
Bioprotection mechanisms by specific binding of globo-series glycosphingolipids to LPS receptors
| Project/Area Number |
23659171
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
FURUKAWA Koichi 名古屋大学, 医学(系)研究科(研究院), 教授 (80211530)
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| Project Period (FY) |
2011 – 2012
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| Keywords | グロボシド / LPS / エンドトキシンショック / A4GALT / TLR-4 |
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| Research Abstract |
Bioprotective functions and action mechanisms of glycosphingolipids induced by LPS were analyzed. In particular, demonstration of novel functions of glycolipids was aimed by analyzing binding specificity and interaction between LPS receptors and Gb4 with focus on the suppressive function of globo-series glycolipids to LPS cytotoxicity. Specific binding of Gb4 to TLR-4/MD2 and the suppression of LPS signals with Gb4 were observed. The fact that only Gb4 with saturated forms of fatty acids bound to TLR-4/MD2 as well as results of immunocytochemistry and of fractionation of membrane molecules suggested that the binding occurred in lipid rafts. Administration of Gb4 into LPS-injected mice could restore them from endotoxin shock, suggesting the possibility of therapeutic application of Gb4 in the clinical fields.
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[Journal Article] TLR4-MD-2complex is negativerly regulated by an endogenous ligand, globotetrasylceramide in vascular endothelial cells2013
Author(s)
Kondo, Y., Tokuda, N., Nishitani, C., Ohto, U., Akashi-takaura, S., Ito, Y., Uchikawa, M., Kuroki, Y., Miyake, K., Zhang, Q., Furukawa, K., Furukawa, K
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Journal Title
Proc. Natl. Acad. Sci. USA
Volume: 110
Pages: 4714-4719
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[Journal Article] Protemic analysis of ganglioside-associated membrane molecules : Substantial basis for molecular clustering2012
Author(s)
Hashimoto, N., Hamamura, K., Kotani, N., Furukawa, K., Kaneko, K., Honke, K., Furukawa, K
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Journal Title
Proteomics
Volume: 12
Pages: 3154-3163
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[Journal Article] Clostridium perfringens Alpha-toxin Recognnezies the GM1a/TrkA Complex2012
Author(s)
Oda, M., Kabura, M., Takagishi, T., Suzue, A., Tominaga, K., Urano, S., Nagahama, M., Kobayashi, K., Furukawa, K., Sakurai, J
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Journal Title
J. Biol. Chem
Volume: 287
Pages: 33070-33079
Peer Reviewed
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[Presentation] TLR4-MD-2 Complex is Negatively Regulated by Endgenous Ligand, Globotetraosylceramide in Vascular Endothelial Cells2012
Author(s)
Furukawa, K., Kondo, Y., Ohto, U., Akashi-Takamura, S., Ito, Y., Miyabe, K., Furukawa, K
Organizer
Symposium in the 35th Annual Meeting of the Molecular Biology Society of Japan "Glycans as disease modifier"
Place of Presentation
福岡国際会議場 福岡市
Year and Date
2012-12-12
Invited
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[Presentation] Roles of globo-series glycolipids in the regulation of LPS-TLR4 signals2012
Author(s)
Furukawa, K., Kondo, Y., Tokuda, N., Ito, Y., Akashi-Takamura, S., Miyabe, K., Furukawa, K
Organizer
ICHC2012 14th International Congress of Histochemistry and Cytochemistry
Place of Presentation
京都国際会議場 京都市
Year and Date
2012-08-26
Invited
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