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2009 Fiscal Year Final Research Report

Shear-stress-induced molecular dynamics of endothelial cell membrane

Research Project

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Project/Area Number 19300155
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionThe University of Tokyo

Principal Investigator

YAMAMOTO Kimiko  The University of Tokyo, 大学院・医学系研究科, 講師 (00323618)

Co-Investigator(Kenkyū-buntansha) ANDO Joji  獨協医科大学, 医学部, 特任教授 (20159528)
Project Period (FY) 2007 – 2009
Keywords血管 / 剪断応力 / 内皮細胞 / カルシウム・シグナリング / メカノトランスダクション / ATP合成酵素 / カベオラ
Research Abstract

Endothelial cells (ECs) release ATP in response to shear stress, a mechanical force generated by blood flow, and the ATP released modulates EC functions through activation of purinoceptors. In this study, we have demonstrated that cell-surface ATP synthase is involved in shear-stress-induced ATP release. Immunofluorescence staining of human pulmonary artery ECs (HPAECs) showed that cell-surface ATP synthase is distributed in lipid rafts and co-localized with caveolin-1, a marker protein of caveolae. Immunoprecipitation indicated that the cell-surface ATP synthase and caveolin-1 are physically associated. Measurement of the extracellular metabolism of ^3H-labeled ADP confirmed that cell surface ATP synthase is active in ATP generation. When exposed to shear stress, HPAECs released ATP in a dose-dependent manner, and the ATP release was markedly suppressed by membrane-impermeable ATP synthase inhibitors, angiostatin and piceatannol, and by an anti-ATP synthase antibody. Depletion of plasma membrane cholesterol with methyl-β cyclodextrin (MβCD) disrupted lipid rafts and abolished co-localization of ATP synthase with caveolin-1, which resulted in a marked reduction in shear-stress-induced ATP release. Down-regulation of caveolin-1 expression by transfection of caveolin-1 siRNA also markedly suppressed ATP-releasing responses to shear stress. These results suggest that the localization and targeting of ATP synthase to caveolae/lipid rafts, is critical for shear stress-induced ATP release by HPAECs.

  • Research Products

    (23 results)

All 2010 2009 2008 2007 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (16 results) Remarks (1 results)

  • [Journal Article] Vascular Mechanobiology : Endothelial Cell Responses to Fluid Shear Stress2009

    • Author(s)
      J. Ando, K. Yamamoto
    • Journal Title

      Circ. J 73

      Pages: 1983-1992

    • Peer Reviewed
  • [Journal Article] Shear stress increases expression of the arterial endothelial markear ephrinB2 in murine ES cells via the VEGF-Notch signaling pathways2009

    • Author(s)
      T. Masumura, K. Yamamoto, N. Shimizu, S. Obi, J. Ando
    • Journal Title

      Arterioscler. Thromb. Vasc. Biol 29

      Pages: 2125-2131

    • Peer Reviewed
  • [Journal Article] Fluid shear stress induces arterial differentiation of endothelial progenitor cells2009

    • Author(s)
      S. Obi, K. Yamamoto, N. Shimizu, S. Kumagaya, T. Masumura, T. Sokabe, T. Asahara, J. Ando
    • Journal Title

      J. Appl. Physiol 106

      Pages: 203-211

    • Peer Reviewed
  • [Journal Article] Cyclic strain induces mouse embryonic stem cell differentiation into vascular smooth muscle cells by activating PDGF receptor β2008

    • Author(s)
      N. Shimizu, K. Yamamoto, S. Obi, S. Kumagaya, T. Masumura, Y. Shimano, K. Naruse, J. K. Yamashita, T. Igarashi, J. Ando
    • Journal Title

      J. Appl. Physiol 104

      Pages: 766-772

    • Peer Reviewed
  • [Journal Article] Differential gene responses in endothelial cells exposed to a combination of shear stress and cyclic stretch2008

    • Author(s)
      M. Toda, K. Yamamoto, N Shimizu, S. Obi, S. Kumagaya, T. Igarashi, A. Kamiya, J. Ando
    • Journal Title

      J. Biothechnol 133

      Pages: 239-244

    • Peer Reviewed
  • [Journal Article] Involvement of cell surface ATP synthase in flow-induced ATP release by vascular endothelial cells2007

    • Author(s)
      K. Yamamoto, N. Shimizu, S. Obi, S. Kumagaya, Y. Taketani, A. Kamiya, J. Ando
    • Journal Title

      Am. J. Physiol Heart Circ. Physiol 293

      Pages: 1646-1653

    • Peer Reviewed
  • [Presentation] 血管内皮のカルシウムシグナリングを介した血流感知機構2010

    • Author(s)
      山本希美子, 安藤譲二
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      岡山
    • Year and Date
      2010-03-28
  • [Presentation] 血管内皮細胞における血流感知機構2010

    • Author(s)
      山本希美子, 安藤譲二
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪
    • Year and Date
      2010-03-16
  • [Presentation] 内皮細胞のシェアストレス応答と循環機能調節2009

    • Author(s)
      山本希美子, 安藤譲二
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-10
  • [Presentation] 血流刺激による血管細胞の分化誘導2009

    • Author(s)
      山本希美子, 安藤譲二
    • Organizer
      第17回日本血管生物医学会
    • Place of Presentation
      東京
    • Year and Date
      2009-10-09
  • [Presentation] Fluid-mechanical force-induced differentiation of murine ES cells towards vascular cells2009

    • Author(s)
      K. Yamamoto, T. Masumura, N. Shimizu, A. Kamiya, J. Ando
    • Organizer
      The Third Switzerland-Japan Workshop on Biomechanics 2009
    • Place of Presentation
      Engelberg
    • Year and Date
      2009-09-04
  • [Presentation] Shear Stress Mechanotransduction via Endothelial ATP Receptors and its Physiological Role in the Vascular System2009

    • Author(s)
      J. Ando, K. Yamamoto
    • Organizer
      The 36^<th> International Congress of Physiological Science
    • Place of Presentation
      Kyoto
    • Year and Date
      2009-07-31
  • [Presentation] Endothelial P2X4-mediated shear-stress-mechanotransduction and its roles in the control of vascular functions Fukuoka Purine 20092009

    • Author(s)
      K. Yamamoto, J. Ando
    • Organizer
      Joint with JSPS Core-to-Core Program A Satellite Symposium for IUPS 2009
    • Place of Presentation
      Fukuoka
    • Year and Date
      2009-07-23
  • [Presentation] Shear stress induces arterial differentiation of murine ES cells via the VEGF-Notch signaling2009

    • Author(s)
      K. Yamamoto, N. Shimizu, T. Masumura, J. Ando
    • Organizer
      The 14^<th> Meeting on Thrombosis & Rheology
    • Place of Presentation
      Tokyo
    • Year and Date
      2009-03-14
  • [Presentation] カルシウムシグナリングを介した血管内皮のメカノトランスダクション2008

    • Author(s)
      山本希美子, 安藤譲二
    • Organizer
      BMB2008 (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
      2008-12-12
  • [Presentation] 血管内皮細胞の流れずり応力依存的な内因性ATP放出2008

    • Author(s)
      山本希美子, 古屋喜四夫, 曽我部正博, 安藤譲二
    • Organizer
      生理学研究所研究会 病態と細胞外プリン-治療標的としての可能性を探る-
    • Place of Presentation
      岡崎
    • Year and Date
      2008-09-04
  • [Presentation] 機械刺激によるATP放出のリアルタイムイメージング2008

    • Author(s)
      古屋喜四夫, 山本希美子, 古屋園子, 塞藤譲二, 曽我部正博
    • Organizer
      生理学研究所研究会
    • Place of Presentation
      岡崎
    • Year and Date
      2008-09-04
  • [Presentation] 内皮細胞のATP受容体を介した血流センシング2008

    • Author(s)
      山本希美子, 安藤譲二
    • Organizer
      第31回バイオレオロジー学会年会
    • Place of Presentation
      東京
    • Year and Date
      2008-06-05
  • [Presentation] Fluid shear stress induces arterial differentiation of endothelial progenitor cells2008

    • Author(s)
      Syotaro Obi, Kimiko Yamamoto, Joji Ando
    • Organizer
      The 13^<th> Meeting on Thrombosis & Rheology
    • Place of Presentation
      Tokyo
    • Year and Date
      2008-03-15
  • [Presentation] 血管内皮細胞における勇断応力のメカノトランスダクション2007

    • Author(s)
      山本希美子, 安藤譲二
    • Organizer
      第55回レオロジー討論会
    • Place of Presentation
      金沢
    • Year and Date
      2007-11-01
  • [Presentation] 血管のバイオメカニクス2007

    • Author(s)
      山本希美子
    • Organizer
      滋賀経済産業協会 ニューマテリアル研究会
    • Place of Presentation
      大津
    • Year and Date
      2007-10-18
  • [Presentation] 血管内皮のATPレセプターを介したメカノトランスダクション2007

    • Author(s)
      山本希美子
    • Organizer
      豊田理化学研究所特定課題研究「細胞の力学機構応答」討論会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-10-12
  • [Remarks] ホームページ等

    • URL

      http://bme-sysphysiol.m.u-tokyo.ac.jp/

URL: 

Published: 2011-06-18   Modified: 2016-04-21  

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