| Project/Area Number |
62480127
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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 |
General medical chemistry
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| Research Institution | Tokushima University |
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Principal Investigator |
YAMAMOTO Shozo Tokushima University School of Medicine, Professor, 医学部, 教授 (50025607)
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| Co-Investigator(Kenkyū-buntansha) |
吉本 谷博 徳島大学, 医学部, 助教授 (60127876)
UEDA Natsuo Tokushima University School of Medicine, Lecturer, 医学部, 講師 (20193807)
HAYASHI Yoko Tokushima University School of Medicine, Research Associate, 医学部, 助手 (60035441)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1988: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1987: ¥5,100,000 (Direct Cost: ¥5,100,000)
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| Keywords | Lipoxygenase / Prostaglandin / Thromboxane / Leukotriene / Lipoxin / Leukocyte / モノクローン抗体 / プロスタグランジン・トロンボキサン / アラキドン酸 |
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| Research Abstract |
Lipoxygenases oxygenate arachidonic acid, and the hydroperoxy products are further transformed to bioactive compounds such as prostaglandin, thromboxane and leukotriene. This research project aims to elucidate the molecular and catalytic properties of these mammalian lipoxygenases and to study the dynamics of the enzymes and their regulatory mechanism with reference to the pathogenesis of various diseases.
1) Enzymological studies on lipoxygenases: We investigated the catalytic properties of the immunoaffinity-purified 5- and 12-lipoxygenases of porcine leukocytes. Especially we demonstrated the enzymatic synthesis of lipoxins by the aerobic or anaerobic reaction of the enzymes with 5,15-dihydroperoxy acid.
2) Study on selective lipoxygenase inhibitors: A flavone compound, cirsiliol, which we earlier found as a 5-lipoxygenase inhibitor, was further derivatized for a more potent and water-soluble inhibitor of 5-lipoxygenase, and a phosphate ester of 5-hexyloxy-cirsiliol was prepared. The leukotrienece synthesis in gerbil brain subjected to ischemia followed by reperfusion, was inhibited by administration of the water-soluble flavonoid.
3) Immunohistochemical studies on lipoxygenases: The enzyme immunoassay ststems were developed for quantitative determination of 5- and 12-lipoxygenase by the use of their monoclonal antibodies, and applied to the studies on the tissue distribution of the enzymes. In addition to leukocytes 5- and 12-lipoxygenases were found in intestine, lung, lymphnodes, thymus and others. In these tissues the enzyme was detected only in infiltrating leukocytes and resident mast cells. Only in anterior pituitary 12-lipoxygenase was found in its parenchymal cells.
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