| Project/Area Number |
21790133
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Environmental pharmacy
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| Research Institution | Keio University |
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Principal Investigator |
TSUGAWA Hitoshi Keio University, 医学部, 助教 (30468483)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 薬剤耐性 / 酸化ストレス / ferric uptake regulator(Fur) / superoxide dismutase(SOD) / 抗酸化能 / superoxide dismutase (SOD) / 慢性感染 / アミノ酸変異 / 鉄トランスポーター / Ferric uptake regulator (Fur) / superoxide radicals / ピロリ菌 / 抗酸化分子 / Electron Spin Resonance Assay / Electron Spin Resonance(ESR) |
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| Research Abstract |
Metronidazole (Mtz) is a prodrug that is converted to its active form and superoxide radicals are generated. The transcriptional regulator, ferric uptake regulator (Fur), of H.pylori is a direct suppressor of the ironcofactored superoxide dismutase (SodB), which is essential for protection against superoxide attack. In some Mtz-resistant strains, SodB activity is induced in a dose-dependent manner on exposure to Mtz. These Mtz-resistant strains were found to carry amino acids mutation of Fur (C78Y, P114S ; mutant-type Fur). The binding affinity of the mutant-type Fur to the sodB promoter (Fur-Box) was significantly reduced. Our approach demonstrated that SodB expression is derepressed by mutant-type Fur, which is associated with the development of Mtz resistance.
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