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1995 Fiscal Year Final Research Report Summary

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
KeywordsEndothelial cells / Mechanical stimuli / Morphological response / Mechanosensitive channel / Ca-mobilization / Stress fibers / Cell focal adhesion
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

  • Research Products

    (17 results)

All Other

All Publications (17 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1999-03-16  

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