1998 Fiscal Year Final Research Report Summary
Study on the regulatory mechanisms of endothelium-dependent vasoconstriction and growth of vascular cells
| Project/Area Number |
07101002
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | National Cardiovascular Center Research Institute (1997-1998)
Kyoto University (1995-1996) |
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Principal Investigator |
MASAKI Tomoh National Cardiovascular Center Research Institute, Director General, 所長 (60009991)
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| Co-Investigator(Kenkyū-buntansha) |
SAWAMURA Tatsuya National Cardiovascular Center Research Institute, Head, バイオサイエンス部, 室長 (30243033)
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| Project Period (FY) |
1995 – 1998
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| Keywords | vascular endothelium / endothelin / nitric oxide / oxidized LDL / endothelin receptor / vasoconstriction / cell growth, dystroglycan / ジストログリカン |
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| Research Abstract |
To elucidate regulatory role for endothelium in local vascular function. we have studied cellular and subcellular mechanisms of endothelin(ET) action and interaction between ET and nitric oxide(NO). A novel endothelial receptor for oxidized LDL was cloned. It phagocytized the aged blood cells and the apoptized cells as well as oxidized LDL.It also suppressed NO synthesis via inhibition of cationic amino acid transporter, and increased ET synthesis. ET induced smooth muscle contraction by activation of non-selective cation channel sensitive to SK&F96365. This channel was also inhibited by NO.Both ET_A and ET_B coupled to Galphas, Galphai, and Galphaq. However, each of these Galpha proteins bound to different part of the domain of ET receptor. Palmitoylation of C-terminal cystein residues of ET receptor was particularly important to the binding of Galphai and Galphaq. Cell growth activity of ET was mediated by three ways, i.e. activation of protein kinase C, phosphoinositide 3-kinase, and thyrosin kinase pathways. MAP kinase was activated in every pathway. Dystroglycan was shown to be expressed in endothelium. It was shown that dystroglycan regulated motility of endothelial cells.
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Research Products
(35 results)
