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Published on: August 1, 2015
2-Oxo-histidine-containing dipeptides are functional oxidation products
Hideshi Ihara1, Yuki Kakihana1, Akane Yamakage1
1Department of Biological Science, Graduate School of Science, Sakai, Osaka 599-8531, Japan.
Imidazole-containing dipeptides (IDPs) are antioxidants. New research reveals 2-oxo-IDPs are novel antioxidant products found in vivo, offering a new understanding of IDP antioxidant mechanisms.
Area of Science:
- Biochemistry
- Cell Biology
- Neuroscience
Background:
- Imidazole-containing dipeptides (IDPs), like carnosine, possess antioxidant properties.
- The exact mechanisms behind IDP antioxidant activity are not fully understood.
- IDPs are abundant in animal skeletal muscles and nerves.
Purpose of the Study:
- To investigate the mechanisms of antioxidant effects of IDPs.
- To identify novel IDP-related compounds in mammalian tissues.
- To explore the role of these compounds in oxidative stress conditions.
Main Methods:
- High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) analysis.
- Investigation of mouse tissue homogenates and human neuroblastoma cells.
- Exposure of cells to hydrogen peroxide (H2O2) and assessment of cytotoxicity.
Main Results:
- Ubiquitous detection of 2-oxo-histidine-containing dipeptides (2-oxo-IDPs) in mouse tissues.
- Enhanced 2-oxo-IDP production in the brain during sepsis-associated encephalopathy.
- 2-oxo-carnosine demonstrated superior antioxidant activity compared to GSH and ascorbate, inhibiting H2O2-induced cytotoxicity.
Conclusions:
- 2-oxo-IDPs are identified as in vivo metal-catalyzed oxidation products of IDPs.
- Carnosine monooxygenation involves a histidyl-imidazole radical intermediate.
- These findings present a revised understanding of IDP antioxidant functions.
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