| Project/Area Number |
09557182
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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 | 展開研究 |
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| Research Field |
Chemical pharmacy
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| Research Institution | University of Tokushima |
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Principal Investigator |
KUWAHARA Jun (1998-1999) The University of Tokushima, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (90225318)
丹羽 峰雄 (1997) 徳島大学, 薬学部, 教授 (30263867)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Hirokazu Fujisawa Pharmaceutical Co., Ltd., Director, 新薬研究所, 所長
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 1999: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1998: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1997: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | iNOS / NO / Benzoquinone / Vitamin K3 / Triptoquinone / Promoter / 一酸化窒素 / 一酸化窒素合成酵素 / 遺伝子発現 / 転写因子 / ベンゾキノン / 抗炎症・抗リウマチ剤 |
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| Research Abstract |
Nitric oxide (NO) plays an important role in diverse physiological processes, while induction of inducible NO synthease (iNOS) by various stimuli is responsible for pathogenesis of septic shock, and some inflammatory and auto immune diseases. Benzoquinone significantly inhibited NO production in rat C6-glia cell activated by LPS and IFN-γ. Inhibitory effect of benzoquinone might not simply be resulted from redox mechanism, because its two-electron reduced form, hydroquinone also strongly impaired NO production. Of special interest is it that vitamin K3 dramatically increases production of NO by the same stimuli. Mechanistic studies showed that vitamin K3 potentiates the expression of iNOS gene through increase of nuclear entry of NF-kB. In spite of their simple chemical structures, vitamin K3 and benzoquinone have contrary effects on iNOS gene expression. These facts would give useful information on rational design of an new anti-inflammatory and anti-rhymatism drug based on selective inhibition of iNOS activity.
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