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Role of Apolipoprotein E Structure in Disorders of Lipid Metabolism in Brain

Research Project

Project/Area Number 19590048
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionKobe Pharmaceutical University

Principal Investigator

SAITO Hiroyuki  Kobe Pharmaceutical University, 薬学部, 教授 (60300919)

Co-Investigator(Kenkyū-buntansha) 田中 将史  神戸薬科大学, 薬学部, 助教 (40411904)
Co-Investigator(Renkei-kenkyūsha) TANAKA Masafumi  神戸薬科大学, 薬学部, 講師 (40411904)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Keywords生物物理化学 / 脂質代謝異常 / アルツハイマー病 / アポリポタンパク質 / 脂質膜 / グリコサミノグリカン / 薬学
Research Abstract

アポE は、神経細胞でのコレステロール代謝恒常性維持に中心的役割を果たしているタンパク質である。本研究では、アポEの遺伝子多型(アイソフォーム)の一つであるアポE4がアルツハイマー病発症を引き起こす分子機構の解明を目的として、アポE アイソフォームによる脳内コレステロール代謝調節機能の異常を、アイソフォーム間での高次構造変化とそれによる細胞膜脂質や細胞表面糖鎖との相互作用変化などの機能異常に基づいて解析を行った。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (36 results)

All 2009 2008 2007 Other

All Journal Article (15 results) (of which Peer Reviewed: 15 results) Presentation (20 results) Remarks (1 results)

  • [Journal Article] Underlying Apolipoprotein E (ApoE) Isoform-Dependent Lipid Efflux from Neural Cells in Culture.2009

    • Author(s)
      Watanabe, A., Lund-Katz, S., Phillips, M. C., Saito, H., Michikawa, M., Mechanism
    • Journal Title

      J. Neurosci. Res. in press

      Pages: 0-0

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interaction between the N- and C-Terminal Domains Modulates the Stability and Lipid Binding of Apolipoprotein A-I.2009

    • Author(s)
      Koyama, M., Tanaka, M., Dhanasekaran, P., Lund-Katz, S., Phillips, M. C., Saito, H.
    • Journal Title

      Biochemistry 48

      Pages: 2529-2537

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of Lipid-Binding Properties of the N-Terminal Helical Segments in Human Apolipoprotein A-I Using Fragment Peptides.2009

    • Author(s)
      Tanaka, M., Tanaka, T., Ohta, S., Kawakami, T., Konno, H., Akaji, K., Aimoto, S., and Saito, H.
    • Journal Title

      J. Peptide Sci. 15

      Pages: 36-42

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism Underlying Apolipoprotein E (ApoE) Isoform-Dependent Lipid Efflux from Neural Cells in Culture2009

    • Author(s)
      源川博久
    • Journal Title

      Journal of Neuroscience Research (In press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of Peptide-Aldehyde Inhibitors Using R188I Mutant of SARS 3CL Protease as a Proteolysis-Resistant Mutant.2008

    • Author(s)
      Akaji, K., Konno, H., Onozuka, M., Makino, A., Saito, H., Nosaka, K.
    • Journal Title

      Bioorg. Med. Chem. 16

      Pages: 9400-9408

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Conformational Flexibility of the N-terminal Domain of Apolipoprotein A-I Bound to Spherical Lipid Particles.2008

    • Author(s)
      Kono, M., Okumura, Y., Tanaka, M., Nguyen, D., Dhanasekaran, P., Lund-Katz, S., Phillips, M. C., Saito, H.
    • Journal Title

      Biochemistry 47

      Pages: 11340-11347

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Conformational Change of Apolipoprotein A-I and HDL Formation from Model Membranes under Intercellular Acidic Conditions.2008

    • Author(s)
      Fukuda, M., Nakano, M., Miyazaki, M., Tanaka, M., Saito, H., Kobayashi, S., Ueno, M., Handa, T.
    • Journal Title

      J. Lipid Res. 49

      Pages: 2419-2426

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of the N- and C-Terminal Domains in Binding of Apolipoprotein E Isoforms to Heparan Sulfate and Dermatan Sulfate: A Surface Plasmon Study.2008

    • Author(s)
      Yamauchi, Y., Deguchi, N., Takagi, C., Tanaka, M., Dhanasekaran, P., Nakano, M., Handa, T., Phillips, M. C., Lund-Katz, S., Saito, H.
    • Journal Title

      Biochemistry 47

      Pages: 6702-6710

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Contributions of the Carboxyl-Terminal Helical Segment to the Self-Association and Lipoprotein Preferences of Human Apolipoprotein E3 and E4 Isoforms.2008

    • Author(s)
      Sakamoto, T., Tanaka, M., Vedhachalam, C., Nickel, M., Nguyen, D., Dhanasekaran, P., Phillips, M. C., Lund-Katz, S., Saito, H.
    • Journal Title

      Biochemistry 47

      Pages: 2968-2977

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Influence of Tertiary Structure Domain Properties on the Functionality of Apolipoprotein A-I.2008

    • Author(s)
      Tanaka, M., Koyama, M., Dhanasekaran, P., Nguyen, D., Nickel, M., Lund-Katz, S., Saito, H., Phillips, M. C.
    • Journal Title

      Biochemistry 47

      Pages: 2127-2180

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chk1 Is a Histone H3 Threonine 11 Kinase that Regulates DNA Damage-Induced Transcriptional Repression.2008

    • Author(s)
      Shimada, M., Niida, H., Zineldeen, D. H., Tagami, H., Tanaka, M., Saito, H., Nakanishi, M.
    • Journal Title

      Cell 132

      Pages: 221-232

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of the N- and C-Terminal Domains in Binding of Apolipoprotein E Isoforms to Heparan Sulfate and Dermatan Sulfate : A Surface Plasmon Study2008

    • Author(s)
      山内悠子
    • Journal Title

      Biochemistry 47

      Pages: 6702-6710

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Influence of Tertiary Structure Domain Properties on the Functonality of Apolipoprotein A-I2008

    • Author(s)
      田中 将史
    • Journal Title

      Bioehemistry 47

      Pages: 2172-2180

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Contributions of the Carboxyl-Terminal Helical Segment to the Self-Association and Lipoprotein Preferences of Human Apolipoprotein E3 and E4 isoforms2008

    • Author(s)
      阪本 崇彰
    • Journal Title

      Biochemistry 47

      Pages: 2968-2977

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of ATP-Binding Cassette Transporter A1 (ABCA1)-mediated Cellular Lipid Efflux to Apolipoprotein A-I and Formation of High Density Lipoprotein Particles.2007

    • Author(s)
      Vedhachalam, C., Duong, P.T., Nickel, M., Nguyen, D., Dhanasekaran, P., Saito, H., Rothblat, G.H., Lund-Katz, S., Phillips, M. C.
    • Journal Title

      J. Biol. Chem. 282

      Pages: 25123-25130

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Presentation] アポE3N末ドメインの構造と脂質搬出機能に及ぼすダイマー化の影響2009

    • Author(s)
      高木千佳, 源川博久, Lund-Katz, S., Phillips, M. C., 道川誠, 斎藤博幸
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Year and Date
      2009-03-27
    • Related Report
      2008 Final Research Report
  • [Presentation] 環境感受性蛍光プローブ標識によるアポA-IのC末端ヘリックス領域の構造評価2009

    • Author(s)
      小山真央, 田中将史, Lund-Katz, S., Phillips, M.C., 斎藤博幸
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Year and Date
      2009-03-27
    • Related Report
      2008 Final Research Report
  • [Presentation] C末端ヘリックス変異体apoA-I Nichinanの構造と脂質結合性の評価2009

    • Author(s)
      河野百恵, 田中将史, Lund-Katz, S., Phillips, M. C., 斎藤博幸
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Year and Date
      2009-03-27
    • Related Report
      2008 Final Research Report
  • [Presentation] ApoA-I Nichinan脂質搬出機能部位ペプチドの脂質膜との相互作用2009

    • Author(s)
      田中俊充, 岩田真季, 河野百恵, 田中将史, Lund-Katz, S.,斎藤博幸
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Year and Date
      2009-03-27
    • Related Report
      2008 Final Research Report
  • [Presentation] アポE3 N末ドメインの構造と脂質搬出機能に及ぼすダイマー化の影響2009

    • Author(s)
      高木千佳
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Year and Date
      2009-03-27
    • Related Report
      2008 Annual Research Report
  • [Presentation] アポA-I-脂質複合ナノ粒子の創製とその物性・機能評価2008

    • Author(s)
      田中将史, 澤井治子, 坂倉広大, 北川英俊, 奥村優介, 斎藤博幸
    • Organizer
      膜シンポジウム2008
    • Place of Presentation
      豊中
    • Year and Date
      2008-11-14
    • Related Report
      2008 Final Research Report
  • [Presentation] ヒトSerum Amyloid AのN末端領域は脂質結合に重要な役割を果たす2008

    • Author(s)
      大田慎也, 田中将史, 川上徹, 相本三郎, 斎藤博幸
    • Organizer
      第45回ペプチド討論会
    • Place of Presentation
      東京
    • Year and Date
      2008-10-29
    • Related Report
      2008 Final Research Report
  • [Presentation] ヒトapoA-I C末端ペプチドの脂質結合における-アミノ酸欠失の影響2008

    • Author(s)
      田中俊充, 中寺麻理子, 岩田真季, 田中将史
    • Organizer
      第45回ペプチド討論会
    • Place of Presentation
      東京
    • Year and Date
      2008-10-29
    • Related Report
      2008 Final Research Report
  • [Presentation] 急性期タンパク質血清アミロイドA(SAA)の脂質結合部位の特定2008

    • Author(s)
      大田慎也, 田中将史, 川上徹, 相本三郎, 斎藤博幸
    • Organizer
      第58回日本薬学会近畿支部大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-10-25
    • Related Report
      2008 Final Research Report
  • [Presentation] 低HDL血症apoA-I変異体の脂質結合部位ペプチドの構造と機能評価2008

    • Author(s)
      田中俊充, 中寺麻理子, 岩田真季, 田中将史, 杉浦眞喜子, Lund-Katz, S., 斎藤博幸
    • Organizer
      第58回日本薬学会近畿支部大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-10-25
    • Related Report
      2008 Final Research Report
  • [Presentation] 単一トリプトファン変異体を用いたアポEアイソフォームC末ドメインの構造評価2008

    • Author(s)
      高木千佳, 岡田愛弓, 奥村優介, 田中将史, Lund-Katz, S., Phillips, M.C., 斎藤博幸
    • Organizer
      第30回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      札幌
    • Year and Date
      2008-08-07
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] 低HDL血症変異体apoA-I Milano(R173C)の水溶液構造と脂質結合性2008

    • Author(s)
      河野百恵, 坂倉広大, 田中将史, Lund-Katz, S., Phillips, M.C., 斎藤博幸
    • Organizer
      第30回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      札幌
    • Year and Date
      2008-08-07
    • Related Report
      2008 Final Research Report
  • [Presentation] ヒト/マウスキメラ型アポA-Iを用いたN末-C末ドメイン間相互作用の解析2008

    • Author(s)
      小山真央, 木澤愛実, 田中将史, Lund-Katz, S., Phillips, M.C., 斎藤博幸
    • Organizer
      第30回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      札幌
    • Year and Date
      2008-08-07
    • Related Report
      2008 Final Research Report
  • [Presentation] アポA-Iの脂質結合性に及ぼすN末及びC末ドメイン構造の影響2008

    • Author(s)
      斎藤博幸, 小山真央, 田中将史, Lund-Katz, S., Phillips, M. C.
    • Organizer
      日本膜学会第30年会
    • Place of Presentation
      東京
    • Year and Date
      2008-05-16
    • Related Report
      2008 Final Research Report
  • [Presentation] アポリポ蛋白質EのN末、C末ドメインのグリコサミノグリカン結合性への寄2008

    • Author(s)
      出口敬子, 山内悠子, 中野実, 半田哲郎, 斎藤博幸
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-28
    • Related Report
      2008 Final Research Report
  • [Presentation] C末端単一トリプトファン変異体を用いたアポE-脂質複合体の構造評価2008

    • Author(s)
      奥村優介, 高木千佳, 田中将史, Lund-Katz, S., 斎藤博幸
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-28
    • Related Report
      2008 Final Research Report
  • [Presentation] フラグメントペプチドを用いた血清アミロイドA(SAA)各領域の脂質結合性の比較2008

    • Author(s)
      大田慎也, 田中将史, 川上徹, 相本三郎, 斎藤博幸
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-28
    • Related Report
      2008 Final Research Report
  • [Presentation] C末端フラグメントペプチドによるapoA-I Nichinan変異体の構造と脂質結合性の評価2008

    • Author(s)
      田中俊充, 久留島祐未, 田中将史, 杉浦眞喜子, Lund-Katz, S., 斎藤博幸
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-28
    • Related Report
      2008 Final Research Report
  • [Presentation] C末端単-トリプトファン変異体を用いたアポE-脂質複合体の構造評価2008

    • Author(s)
      奥村 優介
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-28
    • Related Report
      2007 Annual Research Report
  • [Presentation] マウスアポA-Iにおけるドメイン構造と脂質結合性2007

    • Author(s)
      斎藤博幸, 小山真央, 田中将史, Lund-Katz, S., Phillips, M.C.
    • Organizer
      第29回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      仙台
    • Year and Date
      2007-11-26
    • Related Report
      2008 Final Research Report
  • [Remarks]

    • URL

      http://www.kobepharma-u.ac.jp/~biophys/

    • Related Report
      2008 Final Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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