Mechanisms of increased vascular permeability associated with sympathetic excitability and the development of treatment strategy of ARDS.
| Project/Area Number |
16390448
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Nagoya University |
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Principal Investigator |
SHIMADA Yasuhiro Nagoya University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (50028669)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Naohisa Aichi Medical University School of Medicine, Professor, 医学部, 教授 (80109321)
NISHIWAKI Kimitoshi Nagoya University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (10189326)
佐藤 光晴 名古屋大学, 医学部附属病院, 講師 (10235343)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2004: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | ARDS / neurogenic pulmonary edema / vascular permeability / vascular regeneration / vascular endothelial cell proliferation / neuropeptide Y / NPYY_3 receptor / Abelson tyrosine kinase / NPY Ya-受容体 / Abelson tyrosine kinase / ニューロペプタイドY / 大動脈内皮細胞 / 低酸素暴露 / 肺水腫 / 血管内皮細胞 / 細胞増殖 / 低酸素状態 / Ab1 / actin polymeration |
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| Research Abstract |
Diseases such as adult respiratory distress syndrome (ARDS) have increased pulmonary vascular permeability in its entity and treatment strategy is fundamental importance. We have previously reported in the neurogenic pulmonary edema rats that a substance (neuropeptide y: NPY) coexisting with norepinephrine in the sympathetic nerves exerts vascular permeability. We have further elucidated the relationship between NPY and vascular permeability in the present research.
1) Abelson tyrosine kinase (Abl) and vascular permeability
Abl is one of the protein phosphorylation enzymes related with actin polymerization and intranuclear protein synthesis (transcription factor). Non-specific inhibitors of Abl decreased vascular permeability caused by NPY.
2) NPY and cell proliferation
It has been reported that vascular endothelial cell proliferation is closely related with vascular permeability. We have shown that in high NPY, hypoxia increased cell proliferation, whereas normal oxygen concentration caused no proliferation. In low NPY, neither hypoxia nor normal oxygen concentration caused proliferation. As in increased vascular permeability, NPY increased vascular cell proliferation by activation of phospholipase C through protein G and activations of protein kinase C and calmodulin-dependent phosphrylation enzyme.
3) Cloning of NPY Y_3 receptor
We have found that the increased proliferation of vascular endothelial cells in hypoxia in the presence of NPY was through NPY Y_3 receptor as was found in increased vascular permeability. However, NPY Y_3 receptor is the only subtype of NPY which has unknown amino acids arrangement. In the NPY Y3 receptor, there would be a chance of transformation of the NPY Y_2 receptor.
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Report
(4 results)
Research Products
(25 results)
