| Project/Area Number |
14570113
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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 | Kyoto Women's University |
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Principal Investigator |
YAMAMOTO Shozo Kyoto Women's University, Faculty of Home Economics, Department of Food and Nutrition, Professor, 家政学部, 教授 (50025607)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Arachidonic acid / Essential fatty acid / Prostaglandin / Lipid mediator / Oxygenase / Cyclooxygenase / Lipoxygenase / Enzyme inhibitor / 酵素免疫測定法 |
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| Research Abstract |
The biosynthesis of lipid mediators from arachidonic acid is initiated by cyclooxygenase and lipoxygenase enzymes. The purpose of this research project is to search for inhibitors of the catalytic activities of these enzymes and the transcription of enzyme genes.
1)Transcription inhibitor of cyclooxygenase gene : Earlier we reported that humulone isolated from beer hop inhibited the transcription of cyclooxygenase-2 gene. In connection of the role of cyclooxygenase-2 in angiogenesis, we found that the angiogenesis of chicken embryo chorioallantoic membrane was markedly inhibited by humulone.
2)12-Lipoxygenase inhibitor : Earlier we found that hinokitiol, a tropolon derivative, was a selective inhibitor of the platelet-type among the three isozymes of 12-lipoxygenase ; platelet-, leukocyte- and epidermis-types. Further studies demonstrated a higher specificity of the inhibition of platelet 12-lipoxygenase with an ether of hinokitiol and cinnamic alcohol. Furthermore, we noted the antioxidant activity of tea leaf catechins, and tested them as an inhibitor of 12-lipoxygenase. Most catechins tested inhibited the enzyme of platelet-type relatively selectively. The most potent and selective inhibition was observed with (-)-gallocatechin gallate with an IC50 of 0.1μM. In addition, hinokitiol at about 10μM inhibited the growth of various cell lines of melanoma and prostate cancer
3)Enzyme immunoassay of prostaglandin E2 : Among various cyclooxygenase-metabolites of arachidonic acid, prostaglandin E2 shows a variety of biological activities, and its production is assayed to follow the cyclooxygenase expression. As an easy and sensitive assay, we attempted to develop an enzyme immunoassay of prostaglandin E2. We developed an assay with acetylcholine esterase as a label which gave a calibration curve with an IC50 of 4.5 pg/50 μl sample.
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