2-Oxo-histidine-containing dipeptides are functional oxidation products

Hideshi Ihara, Yuki Kakihana, Akane Yamakage, Kenji Kai, Takahiro Shibata, Motohiro Nishida, Ken-Ichi Yamada, Koji Uchida

研究成果: ジャーナルへの寄稿記事

抄録

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.

元の言語英語
ページ(範囲)1279-1289
ページ数11
ジャーナルJournal of Biological Chemistry
294
発行部数4
DOI
出版物ステータス出版済み - 1 1 2019

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Carnosine
Dipeptides
Histidine
Oxidation
Antioxidants
Tissue
Anserine
Metals
Electrospray ionization
Molecular oxygen
Scavenging
Cytotoxicity
Chelation
Neuroblastoma
Free Radicals
Muscle
Brain
Animals
Skeletal Muscle
High Pressure Liquid Chromatography

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Ihara, H., Kakihana, Y., Yamakage, A., Kai, K., Shibata, T., Nishida, M., ... Uchida, K. (2019). 2-Oxo-histidine-containing dipeptides are functional oxidation products. Journal of Biological Chemistry, 294(4), 1279-1289. https://doi.org/10.1074/jbc.RA118.006111

2-Oxo-histidine-containing dipeptides are functional oxidation products. / Ihara, Hideshi; Kakihana, Yuki; Yamakage, Akane; Kai, Kenji; Shibata, Takahiro; Nishida, Motohiro; Yamada, Ken-Ichi; Uchida, Koji.

:: Journal of Biological Chemistry, 巻 294, 番号 4, 01.01.2019, p. 1279-1289.

研究成果: ジャーナルへの寄稿記事

Ihara, H, Kakihana, Y, Yamakage, A, Kai, K, Shibata, T, Nishida, M, Yamada, K-I & Uchida, K 2019, '2-Oxo-histidine-containing dipeptides are functional oxidation products' Journal of Biological Chemistry, 巻. 294, 番号 4, pp. 1279-1289. https://doi.org/10.1074/jbc.RA118.006111
Ihara, Hideshi ; Kakihana, Yuki ; Yamakage, Akane ; Kai, Kenji ; Shibata, Takahiro ; Nishida, Motohiro ; Yamada, Ken-Ichi ; Uchida, Koji. / 2-Oxo-histidine-containing dipeptides are functional oxidation products. :: Journal of Biological Chemistry. 2019 ; 巻 294, 番号 4. pp. 1279-1289.
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