Differential metabolomics reveals ophthalmic acid as an oxidative stress biomarker indicating hepatic glutathione consumption

Tomoyoshi Soga, Richard Baran, Makoto Suematsu, Yuki Ueno, Satsuki Ikeda, Tadayuki Sakurakawa, Yuji Kakazu, Takamasa Ishikawa, Martin Robert, Takaaki Nishioka, Masaru Tomita

研究成果: Article査読

504 被引用数 (Scopus)

抄録

Metabolomics is an emerging tool that can be used to gain insights into cellular and physiological responses. Here we present a metabolome differential display method based on capillary electrophoresis time-of-flight mass spectrometry to profile liver metabolites following acetaminophen-induced hepatotoxicity. We globally detected 1,859 peaks in mouse liver extracts and highlighted multiple changes in metabolite levels, including an activation of the ophthalmate biosynthesis pathway. We confirmed that ophthalmate was synthesized from 2-aminobutyrate through consecutive reactions with γ-glutamylcysteine and glutathione synthetase. Changes in ophthalmate level in mouse serum and liver extracts were closely correlated and ophthalmate levels increased significantly in conjunction with glutathione consumption. Overall, our results provide a broad picture of hepatic metabolite changes following acetaminophen treatment. In addition, we specifically found that serum ophthalmate is a sensitive indicator of hepatic GSH depletion, and may be a new biomarker for oxidative stress. Ourmethod can thus pinpoint specific metabolite changes and provide insights into the perturbation of metabolic pathways on a large scale and serve as a powerful new tool for discovering low molecular weight biomarkers.

本文言語English
ページ(範囲)16768-16776
ページ数9
ジャーナルJournal of Biological Chemistry
281
24
DOI
出版ステータスPublished - 2006 6 16

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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