2017 Fiscal Year Final Research Report
Redox-metabolomic analysis of histidine and imidazole dipeptides
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 |
Research Field |
Biomolecular chemistry
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Research Institution | Osaka Prefecture University |
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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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 |
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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Free Research Field |
神経化学、レドックスバイオロジー
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