Structural library and visualization of endogenously oxidized phosphatidylcholines using mass spectrometry-based techniques

• Published in: Nature communications Vol. 12; no. 1; p. 6339
• Main Authors: Matsuoka, Yuta, Takahashi, Masatomo, Sugiura, Yuki, Izumi, Yoshihiro, Nishiyama, Kazuhiro, Nishida, Motohiro, Suematsu, Makoto, Bamba, Takeshi, Yamada, Ken-ichi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.11.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/1647/245/2160; 631/1647/296; 631/45/287/1194; 631/45/608; Acetaminophen; Acetaminophen - adverse effects; Analgesics; Analytical methods; Animals; Cytochrome; Cytochrome P-450 CYP2E1 - metabolism; Cytochrome P450; Cytochromes P450; Fatty acids; Fatty Acids, Unsaturated; Glutathione; Hepatocytes; Humanities and Social Sciences; Hybridization; Ionization; Ions; Libraries; Lipid peroxidation; Lipidomics - methods; Lipids; Liver; Liver - diagnostic imaging; Liver - injuries; Liver - metabolism; Liver diseases; Male; Mass spectrometry; Mass Spectrometry - methods; Mass spectroscopy; Mice; Mice, Inbred C57BL; Molecular Imaging - methods; multidisciplinary; Oxidation-Reduction; Peroxidation; Phosphatidylcholines - chemistry; Phospholipids - chemistry; Polyunsaturated fatty acids; RAW 264.7 Cells; Science; Science (multidisciplinary); Scientific imaging; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectroscopy; Visualization
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-26633-w

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 18 O 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.