Physical Chemistry of Lipid-Apolipoprotein Interaction in HDL Biogenesis

• Project/Area Number: 20790032
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Physical pharmacy
• Research Institution: Kyoto University
• Principal Investigator: NAKANO Minoru Kyoto University, 薬学研究科, 准教授 (70314226)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: コレステロール / アポリポタンパク質 / ABCA1 / HDL / 両親媒性ペプチド

Research Abstract

We investigate apolipoprotein A-I-lipid membrane interaction to elucidate mechanism of the formation of HDLs, which act as anti-atherogenic. We found discoidal lipid-apolipoprotein complexes are spontaneously formed by the change in the lipid compositions and pH at membrane's surface. Structure and lipid dynamics of the discoidal complexes were also evaluated by means of neutron scattering and fluorescence analyses.

Research Products

• [Journal Article] Effects of Phospholipid and Surface Pressure on Lipoprotein Lipase-Lipolysis of Triglyceride in Monolayers. (2010)
  • Author(s): K. Nishitsuji, M. Nakano, S. Morita, T. Handa
  • Journal Title: Membrane 35(1) Pages: 30-36
  • NAID: 10026876983
  • Peer Reviewed
• [Journal Article] Smaller Discoidal High-Density Lipoprotein Particles Form Saddle Surfaces, but Not Planar Bilayers. (2009)
  • Author(s): M. Miyazaki, M. Nakano, M. Fukuda, T. Handa
  • Journal Title: Biochemistry 48(32) Pages: 7756-7763
  • Peer Reviewed
• [Journal Article] Static and Dynamic Properties of Phospholipid Bilayer Nanodiscs. (2009)
  • Author(s): M. Nakano, M. Fukuda, T. Kudo, M. Miyazaki, Y. Wada, N. Matsuzaki, H. Endo, T. Handa
  • Journal Title: J. Am. Chem. Soc. 131(23) Pages: 8308-8312
  • Peer Reviewed
• [Journal Article] Flip-Flop of Phospholipids in Vesicles: Kinetic Analysis with Time-Resolved Small-Angle Neutron Scattering. (2009)
  • Author(s): M. Nakano, M. Fukuda, T. Kudo, N. Matsuzaki, T. Azuma, K. Sekine, H. Endo, T. Handa
  • Journal Title: J. Phys. Chem. B 113(19) Pages: 6745-6748
  • Peer Reviewed
• [Journal Article] Useful Modified Cellulose Polymers as New Emulsifiers of Cubosomes. (2009)
  • Author(s): M. Uyama, M. Nakano, J. Yamashita, T. Handa
  • Journal Title: Langmuir 25(8) Pages: 4336-4338
  • Peer Reviewed
• [Journal Article] Synthetic Pentapeptides Inhibiting Autophosphorylation of Insulin Receptor in a Non-ATP-Competitive Mechanism. (2009)
  • Author(s): M. Kato, M. Abe, Y. Kuroda, M. Hirose, M. Nakano, T. Handa
  • Journal Title: J. Pept. Sci. 15(5) Pages: 327-336
  • Peer Reviewed
• [Journal Article] 静的・動的構造評価による生体脂質複合体形成機構の解明. (2009)
  • Author(s): 中野実
  • Journal Title: Yakugaku Zasshi 129(9) Pages: 1033-1039
  • NAID: 130000136000
  • Peer Reviewed
• [Journal Article] Flip-Flop of Phospholipids in Vesicles : Kinetic Analysis with Time-Resolved Small-Angle Neutron Scattering (2009)
  • Author(s): M.Nakano, M.Fukuda, T.Kudo, N.Matsuzaki, T.Azuma, K.Sekine, H.Endo, T.Handa
  • Journal Title: J.Phys.Chem.B 113 Pages: 6745-6748
  • Peer Reviewed
• [Journal Article] Static and Dynamic Properties of Phospholipid Bilayer Nanodiscs (2009)
  • Author(s): M.Nakano, M.Fukuda, T.Kudo, M.Miyazaki, Y.Wada, N.Matsuzaki, H.Endo, T.Handa
  • Journal Title: J.Am.Chem.Soc. 131 Pages: 8308-8312
  • Peer Reviewed
• [Journal Article] Smaller Discoidal High-Density Lipoprotein Particles Form Saddle Surfaces, but Not Planar Bilayers (2009)
  • Author(s): M.Miyazaki, M.Nakano, M.Fukuda, T.Handa
  • Journal Title: Biochemistry 48 Pages: 7756-7763
  • Peer Reviewed
• [Journal Article] Synthetic Pentapeptides Inhibiting Autophosphorylation of Insulin Receptor in a Non-ATP-Competitive Mechanism (2009)
  • Author(s): M. Kato, M. Abe, Y. Kuroda, M. Hirose, M. Nakano, T. Handa
  • Journal Title: J. Put. Sci. 15 Pages: 327-336
  • Peer Reviewed
• [Journal Article] Cytotoxicity of lipid-free apolipoprotein B. Biochim. (2008)
  • Author(s): S. Morita, Y. Deharu, E. Takata, M. Nakano, T. Handa
  • Journal Title: Biophys. Acta 1778(11) Pages: 2594-2603
  • Peer Reviewed
• [Journal Article] Conformational Change of Apolipoprotein A-I and HDL Formation from Model Membranes under Intracellular Acidic Conditions. (2008)
  • Author(s): M. Fukuda, M. Nakano, M. Miyazaki, M. Tanaka, H. Saito, S. Kobayashi, M. Ueno, T. Handa
  • Journal Title: J. Lipid Res. 49(11) Pages: 2419-2426
  • 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 Resonance Study. (2008)
  • Author(s): Y. Yamauchi, N. Deguchi, C. Takagi, M. Tanaka, P. Dhanasekaran, M. Nakano, T. Handa, M.C. Phillips, S. Lund-Katz, H. Saito
  • Journal Title: Biochemistry 47(25) Pages: 6702-6710
  • Peer Reviewed
• [Journal Article] Inhibition of Autophosphorylation of Epidermal Growth Factor Receptor by a Small Peptide not Employing an ATP-Competitive Mechanism (2008)
  • Author(s): M. Abe, Y. Kuroda, M. Hirose, M. Kato, M. Murakami, Y. Watanabe, M. Nakano, T. Handa
  • Journal Title: Biopolymers 89(1) Pages: 40-51
  • Peer Reviewed
• [Journal Article] アポリポタンパク-脂質膜相互作用によるディスク状複合体形成と高密度リポタンパク質形成原理の考察. (2008)
  • Author(s): 中野実
  • Journal Title: Yakugaku Zasshi 128(5) Pages: 687-693
  • Peer Reviewed
• [Journal Article] SANS-Uを使った脂質のベシクル間移動の研究. (2008)
  • Author(s): 中野実
  • Journal Title: 波紋 18(2) Pages: 82-85
  • 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 Resonance Study (2008)
  • Author(s): Y. Yamauchi, N. Deguchi, C. Takagi, M. Tanaka, P. Dhanasekaran, M. Nakano, T. Handa, M. C. Phillips, S. Lund-Katz, H. Saito
  • Journal Title: Biochemistry 47 Pages: 6702-6710
  • Peer Reviewed
• [Journal Article] Conformational Change of Apolipoprotein A-I and HDL Formation from Model Membranes under Intracellular Acidic Conditions (2008)
  • Author(s): M. Fukuda, M. Nakano, M. Miyazaki, M. Tanaka, H. Saito, S. Kobayashi, M. Ueno, T. Handa
  • Journal Title: J. Lipid Res. 49 Pages: 2419-2426
  • Peer Reviewed
• [Journal Article] Cytotoxicity of lipid-free apolipoprotein B (2008)
  • Author(s): S. Morita, Y. Deharu, E. Takata, M. Nakano, T. Handa
  • Journal Title: Biochim. Biophys. Acta 1788 Pages: 2594-2603
  • Peer Reviewed
• [Presentation] 中性子小角散乱による脂質ナノディスクの構造とダイナミクスの評価 (2009)
  • Author(s): 中野実
  • Organizer: 高分子討論会
  • Place of Presentation: 熊本
  • Year and Date: 2009-09-17
• [Presentation] 中性子小角散乱による脂質ナノディスクの構造とダイナミクスの評価 (2009)
  • Author(s): 中野実
  • Organizer: 第58回高分子討論会
  • Place of Presentation: 熊本
  • Year and Date: 2009-09-17
• [Presentation] 脂質の動的特性の評価とその制御 (2009)
  • Author(s): 中野実
  • Organizer: 拡大IRT研究会
  • Place of Presentation: 東海
  • Year and Date: 2009-08-04
• [Presentation] ディスク状脂質/apoA-I複合体の構造と脂質移動速度の評価 (2009)
  • Author(s): 中野実、宮崎公一、福田正和、半田哲郎
  • Organizer: 脂質生化学会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-07-30
• [Presentation] ディスク状脂質/apoA-I複合体の構造と脂質移動速度の評価 (2009)
  • Author(s): 中野実
  • Organizer: 第51回日本脂質生化学会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-07-30
• [Presentation] 中性子小角散乱のリン脂質膜への適用～構造とダイナミクス～ (2009)
  • Author(s): 中野実
  • Organizer: 中性子バイオ・ソフトマターサイエンスワークショップ
  • Place of Presentation: 東京
  • Year and Date: 2009-07-07
• [Presentation] 中性子小角散乱のリン脂質膜への適用 ～構造とダイナミクス～ (2009)
  • Author(s): 中野実
  • Organizer: 中性子バイオ・ソフトマターサイエンスワークショップ
  • Place of Presentation: 東京
  • Year and Date: 2009-07-07
• [Presentation] 脂質ナノディスクの構造と脂質移動速度の評価 (2009)
  • Author(s): 中野実、福田正和、工藤嵩之、松崎直哉、宮崎公一、半田哲郎
  • Organizer: 膜学会
  • Place of Presentation: 東京
  • Year and Date: 2009-05-21
• [Presentation] 脂質ナノディスクの構造と脂質移動速度の評価 (2009)
  • Author(s): 中野実
  • Organizer: 日本膜学会第31年会
  • Place of Presentation: 東京
  • Year and Date: 2009-05-21
• [Presentation] 脂質膜の構造と動的特性の評価 (2009)
  • Author(s): 中野実
  • Organizer: 次世代スパコン「ナノ統合拠点」連続研究会
  • Place of Presentation: 京都
  • Year and Date: 2009-02-10
• [Presentation] 時分割中性子散乱による膜脂質のダイナミクスの評価 (2008)
  • Author(s): 中野実
  • Organizer: 中性子科学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-12-02
• [Presentation] Lipid Transfer Dynamics in Nanoparticle Systems (2008)
  • Author(s): M. Nakano
  • Organizer: 2008 Julich Soft Matter Days
  • Place of Presentation: Bonn
  • Year and Date: 2008-11-12
• [Presentation] Evaluation of intervesicular transfer and flip-flop of phospholipids by time-resolved small-angle neutron scattering (2008)
  • Author(s): M. Nakano
  • Organizer: ICBL
  • Place of Presentation: Maastricht
  • Year and Date: 2008-08-28
• [Presentation] Evaluation of Intervesicular Transfer and Flip-Flop of Phospholipids by Time-Resolved Small-Angle Neutron Scattering (2008)
  • Author(s): Minoru Nakano, Takayuki Kudo, Masakazu Fukuda. and Tetsurou Banda
  • Organizer: International Conference of Biochemistry of Lipids
  • Place of Presentation: Maastricht (Netherlands)
  • Year and Date: 2008-08-28
• [Presentation] In Situ Determination of Interbilayer and Transbilayer Lipid Transfers in Liposomes (2008)
  • Author(s): M. Nakano
  • Organizer: LRD2008
  • Place of Presentation: Yokohama
  • Year and Date: 2008-07-21
• [Presentation] In Site Determination of Interbilayer and Transbilayer Lipid Transfers in Liposomes (2008)
  • Author(s): 中野実
  • Organizer: 11th Liposome Research Days Conference
  • Place of Presentation: Yokohama
  • Year and Date: 2008-07-21
• [Presentation] 中性子小角散乱を用いた膜脂質のダイナミクス評価 (2008)
  • Author(s): 中野実
  • Organizer: IAP環境技術フォーラム
  • Place of Presentation: 京都
  • Year and Date: 2008-06-01
• [Presentation] コレステロールによるエマルションの表面状態と両親媒性ヘリックス結合性の変化 (2008)
  • Author(s): 小澤真衣、中野実、半田哲郎
  • Organizer: 膜学会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-15
• [Presentation] コレステロールによるエマルションの表面状態と両親媒性ヘリックス結合性の変化 (2008)
  • Author(s): 中野実、小澤真衣、半田哲郎
  • Organizer: 日本膜学会第30年会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-15
• [Presentation] Evaluation of Intervesicular Transfer and Flip-Flop of Phospholipids by Time-Resolved Small-Angle Neutron Scattering (2008)
  • Author(s): M. Nakano
  • Organizer: CTC Kickoff Meeting
  • Place of Presentation: Kyoto
  • Year and Date: 2008-04-12
• [Book] 超分子サイエンス&テクノロジー(国武豊喜監修, キューボソームの調製法と応用) (2009)
  • Author(s): 中野実
  • Publisher: エヌ・ティー・エス
• [Remarks]
  • URL: http://www.pharm.kyoto-u.ac.jp/seizai/
• [Remarks]
  • URL: http://www.pharm.kyoto-u.ac.jp/seizai/