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STRUCTURE-FUNCTION RELATIONSHIP OF CHOLESTEROL-ENRICHED MEMBRANE MICRODOMAINS

Research Project

Project/Area Number 20570116
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionTokyo Metropolitan Institute of Gerontology

Principal Investigator

IWASHITA Yoshiko  Tokyo Metropolitan Institute of Gerontology, 薬学部, 客員研究員 (50111498)

Co-Investigator(Kenkyū-buntansha) IWASHITA Shintaro  いわき明星大学, 薬学部, 教授 (90092147)
INOMATA Mitsushi  地方独立行政法人東京都健康長寿医療センター, 東京都健康長寿医療センター研究所, 研究員 (30142649)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords生体膜 / Tリンパ球 / 膜機能ドメイン / コレステロール / シグナル伝達 / 脂質ラフト / 細胞膜 / 脂質ラフ
Research Abstract

To study the structure-function relationship of membrane microdomains (lipid rafts) involved in signal transduction, we examined the alterations of lipid rafts in an age-associated decline in T-cell receptor signaling. By analyzing resting and stimulated mouse CD4^+ T cells, we found that the following alterations may be related to the age-dependent decline in T-cell receptor signaling : 1) age-dependent alterations in several lipid raft-associated molecules, and resulting dysregulation of a negative SFK (Src family kinase) regulatory system ; 2) age-associated up-regulation of PD-1-positive T cells that exhibit proliferative hyporesponsiveness; 3) altered localization/topology of cholesterol, one of major constituents of lipid rafts.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (25 results)

All 2010 2009 2008

All Journal Article (11 results) (of which Peer Reviewed: 6 results) Presentation (11 results) Book (3 results)

  • [Journal Article] Plasma membrane microdomains in aging disease.2010

    • Author(s)
      岩下淑子, 嶋田有紀子, 林昌美, 猪股光司
    • Journal Title

      Geriatr.Gerontol.Int. 10(suppl.1)

    • NAID

      10027272919

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Use of dansyl-cholestanol as a probe of cholesterol behavior in membranes of living cells.2010

    • Author(s)
      Huang, H., McIntosh, A.L., Atshaves, B.P., Ohno-Iwashita Y., Kier, A.B., Schroeder, F.
    • Journal Title

      J.Lipid Res. 51

      Pages: 1157-1172

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 加齢に伴って増加するPD-1陽性Tリンパ球の正体は?2010

    • Author(s)
      猪股光司、嶋田有紀子、林昌美、岩下淑子
    • Journal Title

      基礎老化研究 34

      Pages: 23-27

    • NAID

      10026103948

    • Related Report
      2010 Final Research Report
  • [Journal Article] Use of dansylcholestanol as a probe of cholesterol behavior in membranes of living cells.2010

    • Author(s)
      Huang, H., et al.
    • Journal Title

      J.Lipid Res.

      Volume: 51 Pages: 1157-1172

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasma membrane microdomains in aging and disease2010

    • Author(s)
      Ohno-Iwashita, Y., et al.
    • Journal Title

      Geriatr.Gerontol.Int.

      Volume: 10

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 加齢に伴って増加するPD-1陽性Tリンパ球の正体は?2010

    • Author(s)
      猪股光司, 他
    • Journal Title

      基礎老化研究 34

      Pages: 23-27

    • NAID

      10026103948

    • Related Report
      2009 Annual Research Report
  • [Journal Article]2010

    • Author(s)
      岩下淑子
    • Journal Title

      新老年学(第3版)(東京大学出版会)

      Pages: 78-84

    • Related Report
      2009 Annual Research Report
  • [Journal Article]2010

    • Author(s)
      Ohno-Iwashita, Y., et al.
    • Journal Title

      Cholesterol Binding and Cholesterol Transport Proteins (Subcellular Biochemistry, Vol.51)(Springer)

      Pages: 597-621

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Age-associated up-regulation of a negative co-stimulatory receptor PD-1 in mouse CD4+ T cells.2009

    • Author(s)
      Shimada Y., Hayashi M., Nagasaka, Y., Ohno-Iwashita Y, Inomata M
    • Journal Title

      Exp.Gerontol. 44

      Pages: 517-522

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Age-associated up-regulation of a negative co-stimulatory receptor PD-1 in mouse CD4+ T cells.2009

    • Author(s)
      Shimada, Y., et al.
    • Journal Title

      Exp.Gerontol. 44

      Pages: 517-522

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article]2008

    • Author(s)
      McInstosh, A. L., et al.
    • Journal Title

      Probes and Tags to Study Biomolecular Function : for proteins, RNA, and Membranes(Wiley-VCH)

      Pages: 1-33

    • Related Report
      2008 Annual Research Report
  • [Presentation] 加齢で増加するPD-1陽性CD4^+T細胞は刺激に対して不応答性である2009

    • Author(s)
      嶋田有紀子, 他
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県)
    • Year and Date
      2009-10-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] 老齢マウスで見いだされた抑制型補助刺激シグナル受容体(PD-1)陽性CD4^+T細胞の性質2009

    • Author(s)
      猪股光司, 他
    • Organizer
      第32回日本基礎老化学会大会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2009-06-19
    • Related Report
      2009 Annual Research Report
  • [Presentation] 老齢マウスで見いだされた抑制型補助刺激シグナル受容体(PD-1)陽性CD4^+T細胞の性質2009

    • Author(s)
      猪股光司、嶋田有紀子、林昌美、岩下淑子
    • Organizer
      第32回日本基礎老化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] 加齢で増加するPD-1陽性CD4^+T細胞は刺激に対して不応答性である2009

    • Author(s)
      嶋田有紀子、林昌美、長坂安彦、岩下淑子、猪股光司
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Related Report
      2010 Final Research Report
  • [Presentation] 老齢マウスT細胞に於ける抑制型補助刺激シグナル受容体PD-1の発現亢進とその意義2008

    • Author(s)
      猪股光司, 他
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] Revisiting lipid saymmetry in red blood cells2008

    • Author(s)
      Murate, M., et al.
    • Organizer
      Flippases 2008
    • Place of Presentation
      Ascona, Switzerland
    • Year and Date
      2008-11-04
    • Related Report
      2008 Annual Research Report
  • [Presentation] Cholesterol gradient in biological membranes2008

    • Author(s)
      Murase-Tamada, K., Murate, M., Hayakawa, T., Nakamura, K., Ito, K., Shimada Y., Ohno-Iwashita Y., Kobayashi, T.
    • Organizer
      International Symposium on Molecular System Life Sciences
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2010 Final Research Report
  • [Presentation] 老齢マウスT細胞に於ける抑制型補助刺激シグナル受容体PD-1の発現充進とその意義2008

    • Author(s)
      猪股光司、嶋田有紀子、林昌美、岩下淑子
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会
    • Place of Presentation
      神戸
    • Related Report
      2010 Final Research Report
  • [Presentation] 加齢に伴って増加するPD-1陽性CD4+T細胞の同定とその特徴2008

    • Author(s)
      嶋田有紀子、猪股光司、林昌美、岩下淑子
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会
    • Place of Presentation
      神戸
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] Revisiting lipid asymmetry in red blood cells2008

    • Author(s)
      Murate, M., Shimada Y., Ohno-Iwashita Y., Umeda, M., Kobayashi, T.
    • Organizer
      Flippases 2008
    • Place of Presentation
      Ascona, Switzerl
    • Related Report
      2010 Final Research Report
  • [Presentation] 老齢マウスTリンパ球に於ける抑制型補助シグナル受容体の発現亢進2008

    • Author(s)
      猪股光司、林昌美、嶋田有紀子、岩下淑子
    • Organizer
      第31回日本基礎老化学会大会
    • Place of Presentation
      松本
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Book] Cholesterol-Binding Toxins Anti-cholesterol Antibodies as Structural Probes for Cholesterol Localization. Vol.51, p.597-621(Harris, J.R.ed.)(Cholesterol Binding Cholesterol Transport Proteins)(Chapter 22) Seies : Subcellular Biochemistry2010

    • Author(s)
      Ohno-Iwashita Y., Shimada, Y., Hayashi, M. Iwamoto, M., Iwashita, S., Inomata, M.
    • Publisher
      Springer
    • Related Report
      2010 Final Research Report
  • [Book] 生体膜の加齢変化、新老年学第3版 p.78-84(大内尉義,秋山弘子編集代表)東京2010

    • Author(s)
      岩下淑子
    • Publisher
      東京大学出版会
    • Related Report
      2010 Final Research Report
  • [Book] Fluorescent sterols to study cholesterol trafficking in living cells. P.1-33(Miller, L.W.ed.)(Probes Tags to Study Biomolecular Function : for Proteins, RNA, Membranes)2008

    • Author(s)
      McIntosh, A.L., Huang, H., Atshaves, B.P., Storey, S.M., Gal legos, A.M., Spencer, T.A., Bittman, R., Ohno-Iwashita, Y., Kier, A.B., Schroeder, F.
    • Publisher
      Wiley-VCH, Weinheim
    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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