| Project/Area Number |
06454665
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biophysics
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| Research Institution | Nagoya University |
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Principal Investigator |
SOKABE Masahiro Nagoya University School of Medicine, Physiology, Professor, 医学部, 教授 (10093428)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| 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)
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| Keywords | Endothelial 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 |
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| 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
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