| Project/Area Number |
16K13089
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomolecular chemistry
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| Research Institution | Osaka Prefecture University |
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Principal Investigator |
Ihara Hideshi 大阪府立大学, 理学(系)研究科(研究院), 准教授 (60254447)
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| Co-Investigator(Renkei-kenkyūsha) |
UCHIDA Koji 東京大学, 大学院農学生命科学研究科, 教授 (40203533)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | レドックスメタボロミクス / メタボローム解析 / イミダゾールジペプチド / 2-オキソ-イミダゾール / 酸化ストレス / レドックスシグナル / オキソヒスチジン |
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| Outline of Final Research Achievements |
Imidazole-containing dipeptides (IDPs), such as carnosine and anserine, show antioxidant activity. However, the underlying mechanisms that could fully explain the antioxidant effects of IDPs remain obscure. We identified 2-oxo- imidazole -containing dipeptides (2-oxo-IDPs) by the LC-ESI-MS/MS analysis. 2-Oxo-IDPs were ubiquitously detected in all mouse tissues examined. Enhanced production of 2-oxo-IDPs was seen in the brain of a mouse model of sepsis-associated encephalopathy. In SH-SY5Y human neuroblastoma cells stably expressing carnosine synthase, H2O2 exposure resulted in the intracellular production of 2-oxo-carnosine, which was associated with significant inhibition of H2O2 cytotoxicity. Mechanistic studies showed that mono-oxygenation of IDPs was mediated through the formation of a histidyl imidazole radical, followed by the addition of molecular oxygen.
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