Structural library and visualization of endogenously oxidized phosphatidylcholines using mass spectrometry-based techniques
Autor: | Makoto Suematsu, Kazuhiro Nishiyama, Yoshihiro Izumi, Masatomo Takahashi, Ken Ichi Yamada, Takeshi Bamba, Yuki Sugiura, Motohiro Nishida, Yuta Matsuoka |
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Rok vydání: | 2021 |
Předmět: |
Male
Science Molecular imaging General Physics and Astronomy Endogeny Mass spectrometry Article General Biochemistry Genetics and Molecular Biology Lipid peroxidation Mice chemistry.chemical_compound medicine Animals Phospholipids Acetaminophen chemistry.chemical_classification Liver injury Multidisciplinary biology Chemistry Liver failure Cytochrome P450 Cytochrome P-450 CYP2E1 General Chemistry medicine.disease Glutathione Mice Inbred C57BL RAW 264.7 Cells Liver Biochemistry Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Lipidomics Fatty Acids Unsaturated Phosphatidylcholines biology.protein Early phase Oxidation-Reduction Polyunsaturated fatty acid |
Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-12 (2021) Nature Communications |
ISSN: | 2041-1723 |
Popis: | Although oxidized phosphatidylcholines (oxPCs) play critical roles in numerous pathological events, the type and production sites of endogenous oxPCs remain unknown because of the lack of structural information and dedicated analytical methods. Herein, a library of 465 oxPCs is constructed using high-resolution mass spectrometry-based non-targeted analytical methods and employed to detect 70 oxPCs in mice with acetaminophen-induced acute liver failure. We show that doubly oxygenated polyunsaturated fatty acid (PUFA)-PCs (PC PUFA;O2), containing epoxy and hydroxide groups, are generated in the early phase of liver injury. Hybridization with in-vivo 18O labeling and matrix-assisted laser desorption/ionization-tandem MS imaging reveals that PC PUFA;O2 are accumulated in cytochrome P450 2E1-expressing and glutathione-depleted hepatocytes, which are the major sites of liver injury. The developed library and visualization methodology should facilitate the characterization of specific lipid peroxidation events and enhance our understanding of their physiological and pathological significance in lipid peroxidation-related diseases. Oxidized phosphatidylcholines (oxPCs) are a structurally diverse class of lipids associated with various diseases. Here, the authors use mass spectrometry to construct a spectral library of 465 oxPCs and subsequently profile oxPCs formed during acetaminophen-induced acute liver failure in mice. |
Databáze: | OpenAIRE |
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