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2017 Fiscal Year Final Research Report

Redox-metabolomic analysis of histidine and imidazole dipeptides

Research Project

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Project/Area Number 16K13089
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Biomolecular chemistry
Research InstitutionOsaka 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)

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)
Project Period (FY) 2016-04-01 – 2018-03-31
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.

Free Research Field

神経化学、レドックスバイオロジー

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Published: 2019-03-29  

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