Journal
ANALYTICAL CHEMISTRY
Volume 92, Issue 10, Pages 6993-7002Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.0c00053
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Funding
- AMED-CREST grant [JP19gm0910013]
- JST PRESTO [JPMJPR1337]
- JSPS KAKENHI [18K14884, 16H01363, 17H03977, 17H06304, 17H06299]
- Naito Foundation
- Daiichi Sankyo Foundation of Life Science
- ONO Medical Research Foundation, Japan
- Grants-in-Aid for Scientific Research [17H06304, 18K14884, 16H01363, 17H03977] Funding Source: KAKEN
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Diversified oxidized-lipid molecules are responsible for inflammation and cell death, including ferroptosis. Lipid radicals are the source of these oxidized lipids, which are the initial key molecules in the lipid peroxidation chain reaction. However, owing to their extremely high reactivity and short half-life, an established detection technique is not available. Here, we propose a high-performance liquid chromatography fluorometry and high-resolution tandem mass spectrometry system combined with a fluorescent probe as a structural analysis method for lipid-derived radicals. We detected 132 lipid-derived radicals, including 111 new species, from five polyunsaturated fatty acids. In addition, a database was constructed for which the initial fatty acid could be determined using the radical structure. Further, 12 endogenous lipid-derived radicals were identified in carcinogen-induced liver cancer mouse models. Therefore, this method and its corresponding database will provide novel insights into mechanisms underlying the lipid peroxidation, including the associated inflammation and ferroptosis.
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