| Project/Area Number |
11670119
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
SUZUKI Keiichiro Hyogo College of Medicine, Professor, 医学部, 教授 (70221322)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Yoshitaka Osaka University Graduate School of medicine, Research Associate, 大学院・医学系研究科・医学部, 助手 (60252657)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | glycocalyx / cell adhesion / reactive oxygen species / endothelial cell / inflammation / cancer metastasis / sugar chain / 好中球 / ヒドロキシルラジカル |
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| Research Abstract |
The adhesion of colon cancer cells (colo201) and neutrophils to endothelial cells which had been briefly exposed to either hypoxanthine/xanthine oxidase, or hydrogen peroxide, or peroxynitrite was analyzed in the absence of de novo protein synthesis. Such treatments accelerated the adhesions of both colo201 cells and neutrophils to endothelial cells. In this study, de novo protein synthesis was blocked by AcD or CHX and no increase of E-selectin, P-selectin, ICAM-1 and thrombomodulin in endothelial cells was observed as judged by a FACS scan analysis using specific antibodies. Therefore, the accelerated cell adhesion is, most likely, due to the direct effect of hydroxyl radicals. These effects were blocked by SOD/catalase or EDTA.The results provided evidence that hydroxyl radicals affect the cell surface of endothelial cells and accelerate cell adhesion. These findings suggest that ROS may well accelerate cell adhesion very rapidly in the rolling of neutrophils or in the metastasis of tumor cells after radiation therapy or chemotherapy, both of which increase ROS production. ROS molecules have very short half lives and strong non-specific effects and as a result they may play an important role in the super acute phase of inflammation, ischemia-reperfusion or cancer metastasis through their effects on cell adhesion.
Next we found that ceruloplasmin (Cp) can remove hydrogen peroxide and lipid hydroperoxide (LOOH) at physiological concentrations of reduced glutathione. The glutathione peroxidase-like activity of Cp together with its ferroxidase activity would completely remove the primary reactants required for both Fenton chemistry and lipid peroxidation. Moreover, Cp binds to extracellular myeloperoxidase (MPO) and prevents MPO making HOCl, a powerful oxidant which will lead to molecular damage. These two findings suggest that Cp may be an important antioxidant protein in lung lining fluid and extracellular spaces.
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