2-Oxo-histidine–containing dipeptides are functional oxidation products
| Autor: | Koji Uchida, Yuki Kakihana, Motohiro Nishida, Ken Ichi Yamada, Takahiro Shibata, Hideshi Ihara, Akane Yamakage, Kenji Kai |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Antioxidant Cell Survival medicine.medical_treatment Anserine Carnosine Biochemistry Antioxidants Mice Neuroblastoma 03 medical and health sciences chemistry.chemical_compound In vivo Tumor Cells Cultured medicine Animals Humans Histidine Carnosine synthase Muscle Skeletal Molecular Biology 030102 biochemistry & molecular biology biology Imidazoles Dipeptides Hydrogen Peroxide Cell Biology Glutathione Oxidants Mice Inbred C57BL 030104 developmental biology chemistry biology.protein Oxidation-Reduction Intracellular Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 294:1279-1289 |
| ISSN: | 0021-9258 |
| Popis: | Imidazole-containing dipeptides (IDPs), such as carnosine and anserine, are found exclusively in various animal tissues, especially in the skeletal muscles and nerves. IDPs have antioxidant activity because of their metal-chelating and free radical-scavenging properties. However, the underlying mechanisms that would fully explain IDP antioxidant effects remain obscure. Here, using HPLC–electrospray ionization–tandem MS analyses, we comprehensively investigated carnosine and its related small peptides in the soluble fractions of mouse tissue homogenates and ubiquitously detected 2-oxo-histidine–containing dipeptides (2-oxo-IDPs) in all examined tissues. We noted enhanced production of the 2-oxo-IDPs in the brain of a mouse model of sepsis-associated encephalopathy. Moreover, in SH-SY5Y human neuroblastoma cells stably expressing carnosine synthase, H(2)O(2) exposure resulted in the intracellular production of 2-oxo-carnosine, which was associated with significant inhibition of the H(2)O(2) cytotoxicity. Notably, 2-oxo-carnosine showed a better antioxidant activity than endogenous antioxidants such as GSH and ascorbate. Mechanistic studies indicated that carnosine monooxygenation is mediated through the formation of a histidyl-imidazole radical, followed by the addition of molecular oxygen. Our findings reveal that 2-oxo-IDPs are metal-catalyzed oxidation products present in vivo and provide a revised paradigm for understanding the antioxidant effects of the IDPs. |
| Databáze: | OpenAIRE |
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