Differential Metabolomics Reveals Ophthalmic Acid as an Oxidative Stress Biomarker Indicating Hepatic Glutathione Consumption*

By Tomoyoshi Soga, R. Baran, M. Suematsu, Y. Ueno, Satsuki Ikeda, Tadayuki Sakurakawa, Yuji Kakazu, Takamasa Ishikawa, M. Robert, T. Nishioka and 1 more. Journal of Biological Chemistry, 2006

677 citations recorded by the source corpus.

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. Our method 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.

Subfields: Biochemistry, Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ac324eb1420c243030e02218d286913a53416a4f

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In Molecular Biology

1. Masahiro Sugimoto
2. David T. W. Wong
3. Tomoyoshi Soga
4. Masaru Tomita
5. A. Hirayama
6. Hidde de Jong

Citations in the corpus

• CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth. (2011, methodology): “Measurements of Amino Acid Contents and Cystine Uptake in Cultured Cells The intracellular contents of amino acids in HCT116 cells were measured by capillary electrophoresis combined with mass spectrometry (CE-MS, Agilent Technology) as previously described (Kinoshita et al., 2007; Soga et al., 2006”
• Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry. (2009, neutral): “algorithms based on dynamic programming (15, 19).”
• Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles (2009, methodology): “2.3 Metabolite standards, instrumentation, and CE-TOF-MS conditions The metabolite standards, instrumentation and CE-TOFMS condition were used in this study as previously described (Soga et al. 2006), with slight modifications in the lock mass system setting.”