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MOLECULAR MECHANISM OF MORPHOLOGICAL RESPONSE TO MECHANICAL STIMULI IN ENDOTHELIAL CELLS

Research Project

Project/Area Number 06454665
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Biophysics
Research InstitutionNagoya University

Principal Investigator

SOKABE Masahiro  Nagoya University School of Medicine, Physiology, Professor, 医学部, 教授 (10093428)

Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1995: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥4,200,000 (Direct Cost: ¥4,200,000)
KeywordsEndothelial cells / Mechanical stimuli / Morphological response / Mechanosensitive channel / Ca-mobilization / Stress fibers / Cell focal adhesion / Fアクチン / 血管内皮 / 伸展刺激 / 細胞内カルシウム / F-アクチン
Research Abstract

Endothelial cells exhibit spindle like shape aligning their longtude parallel with vessel running. This peculiar shape and alignment is isgnificant to prevent the cells from being pealed off by blood flow. However, cultured endothelial cells do not show such shape and alignment. Then what mechanisms do bring about such an adaptive feature in endothelial cells? It is known that mechanical stresses onto the cells, like shear stress and periodic circumferential stetch, by pulsative blood flow are enough to induce such a morphological response in endothelial cells. The altimate goal of this project is to know the inderlying molecular mechanism in mechanically induced morphological response of endothlial cells. Partcularly we aimed to prove our hypothesis on the molecular cascade : periodic stretch*activation of mechanosensitive channels*intracellular Ca-mobilization*reorganization of stress fibers and forcal adhesion*morphological change.
In the first year we concentrated on the early part … More of the cascade, and found that intacellular Ca-mobilization mediated by the activation of Ca-permeable mechanosensitive ion channels is necessary for the morphological response. In the second year we analyzed the relationship between the cell morphological change and the cytoskeletal reoganization following Ca-mobilization. The reoganization process of stress fibers (bundle of F-actins) could be disected into three steps : depolimerization of pre-exisiting F-actin fibers*formation of new actin filaments perpendicuraly to stretch axis*elongation and bundling of actin fibers. Morphological change of the cells proceeded concomitant with the last step of cytoskeletal reoganization that requires Ca-mobilization. In fact Ca-dependent tyrosine phosphorylation of focal adhesion proteins occured during this step. When this phosphorylation was inhibited by drugs, both the cytoskeletal reoganization and the morphological response was completely inhibited. Involvement of kinases and GTP binding proteins in the molecular cascade remains to be solved. Less

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Okada, H., Yoshida, J., Sokabe, M., Wakabayashi, T., Hagiwara, M.: "Suppression of CD44 expression decreases migartiona nd invasion of human glioma cells." Int J Cancer Res,. 66. 1-6 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Akaike, T, Wang, J, & Sokabe, M.: "Optical imaging of neural activities in the rat cingulate cortex in vitro." Neurosciences,. 21. 81-89 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kobuke, Y., Ueda.K., & Sokabe, M.: "Totally synthetic voltage dependent ion channels." Chem.Let.435-436 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tanaka, Y., Kobuke, Y., & Sokabe, M.: "Non-peptide ion channel with a K^+-selective filter." Angew.Chem.(Int Ed Eng),. 36(40). 693-694 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 曽我部 正博、成瀬 恵治、嶽本 和久、: "SAチャネルは細胞の機械センサか?" 蛋白質・核酸・酵素,. 41. 2-13 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 曽我部 正博、成瀬 恵治、山田 恭子、井上 真寿美、浅野 久木、: "機械刺激に対する内皮細胞のCa2+応答と形態応答" 脈管学(Jpn.J.Angiol.). 34. 989-994 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 曽我部 正博、: "イオンチャネルのゲートとゆらぎ、In「生体膜」(葛西、田口編)" 吉岡書店, 47-66 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 曽我部 正博、: "イオンチャネルによる情報変換、In「ナノバイオロジー入門:時間と空間の生物学」(鳴本編)" 講談社, 66-80 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sokabe, M., Nunogaki, K., Naruse, K.: "Stretch activated ion channels : Macroscopic vs.microscopic responses." Progr Cell Res.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Okada, H., Yoshida, J., Sokabe, M., Wakabayashi, T., Hagiwara, M.: "Suppression of CD44 expression decreases migartion and invasion of human glioma cells." Int J Cancer Res. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Akaike, T,Wang, J,& Sokabe, M.: "Optical imaging of neural activities in the rat cingulate cortex in vitro." Neurosciences. 21. 81-89 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kobuke, Y., Ueda.K., & Sokabe, M.: "Totally synthetic voltage dependent ion channels." Chem.Let.435-436 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tanaka, Y., Kobuke, Y., & Sokabe, M.: "Non-peptide ion channel with a K^+-selective filter." Angew.Chem. (Int Ed Eng). 36 (40). 693-694 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sokabe, M., Naruse, K., Takemoto, K.: "SA channels are a mechano sensor of the cell?" Protein, Nucleic acid and Enzyme. 41. 2-13 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sokabe, M., Naruse, K., Yamada, T., Inoue, M., Asano, H.: "Ca-and morphological responses of endothelial cells to mechaniacl stimulations." Jpn.J.Angiol.34. 989-994 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sokabe, M.: Ion channel gate and its fluctuations.In "Biological membranes" (eds.Kasai, M., Taguchiu, T.) Yoshioka Press, Kyoto (in press),

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sokabe, M.: Signal transduction in ion channels.In "Introduction to Nanobiology" (ed.Shimamoto, N.) Khodansha, Tokyo, 66-88 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Okada,H.,Yoshida,J.,Sokabe,M.,Wakabayashi,T.,Hagiwara,M.: "Suppression of CD44 expression decreases migartiona nd invasion of human glioma cells." Int J Cancer Res.66. 1-6 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Akaike,T,Wang,J,& Sokabe,M.: "Optical imaging of neural activities in the rat cingulate cortex in vitro." Neurosciences,. 21. 81-89 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kobuke,Y.,Ueda,k.,& Sokabe,M.: "Totally synthetic voltage dependent ion channels." Chem.Let.435-436 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tanaka,Y.,Kobuke,Y.,& Sokabe,M.: "Non-peptide ion channel with a K^+-selective filter." Angew.Chem.(Int Ed Eng),. 36(40). 693-694 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 曽我部正博、成瀬恵治、嶽本和久、: "SAチャネルは細胞の機械センサか?" 蛋白質・核酸・酵素,. 41. 2-13 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 曽我部正博、: "単一チャネルデータ解析," 生理学雑誌(J Physiol Soc Jpn). 57. 247-260 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 曽我部正博、: "イオンチャネルのゲートとゆらき、In「生体膜」(葛西、田口編)" 吉岡書店, 47-66(167) (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 曽我部正博、: "パッチクランプ法による単一チャネル電流の記録、In「英語論文セミナー 現代の生命科学シリーズ:細胞生物学」(馬淵、ヤマモト編)" 講談社、, 168(113-120) (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Murakami,T,et.al,: "Enzymatic and genetic adaptation of soleus muscle mitochondoria to physical training in rats." Am.J.Physiol.267E. 388-395 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sokabe,M,Hasegawa,N.,& Yamamori,k.: "Aminoglycoside blockade and amphipaths activation of stretch activated ion channels from shick skeletal muscle." Biophys.J.66(No.2). A167 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Naruse,K.,Inoue,M,Yamada,T.,&、 Sokabe,M.: "Ca2+dependent and Gd3+sensitive morpho logical changes of cultured endothelial cellsby cyclic mechanical stretch." The Physiol.37(4). A6 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 曽我部正博、他: "機械刺激に対する内皮細胞のCa2+応答と形態応答" 脈管学(Jpn.J.Angiol.). 34. 989-994 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 曽我部正博、成瀬恵治、山田恭子、嶽本和久: "血管内皮細胞の機械受容チャネルと細胞応答" 血管と内皮(Blood Vessel & Endothelium). 4. 29-38 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sokabe,M.,Nunogaki,K.& Naruse,K.: "Stretch activated ion channels:Macroscopic vs.microscopic responses" Progr Cell Res.(in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] 曽我部正博: "イオンチャネルによる情報交換(In〔ナノバイオロジー入門:時間と空間の生物学」)(嶋本編)" 講談社, 222 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 曽我部正博: "イオンチャネルの機能的再構成In“膜学実験シリーズI"" 共立出版, 424 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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