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Structural library and visualization of endogenously oxidized phosphatidylcholines using mass spectrometry-based
Yuta Matsuoka1, Masatomo Takahashi2, Yuki Sugiura3
1Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan.
Nature Communications
|November 4, 2021
Summary
Researchers identified novel oxidized phosphatidylcholines (oxPCs) in acute liver failure. These specific oxPCs accumulate in injured liver cells, offering new insights into lipid peroxidation in disease.
Area of Science:
- Biochemistry
- Pathology
- Analytical Chemistry
Background:
- Oxidized phosphatidylcholines (oxPCs) are implicated in various diseases.
- The specific types and origins of endogenous oxPCs are largely unknown due to limited analytical tools and structural data.
Purpose of the Study:
- To develop novel analytical methods for identifying and localizing endogenous oxPCs.
- To investigate the role of oxPCs in acetaminophen-induced acute liver failure.
Main Methods:
- Construction of a comprehensive library of 465 oxPCs.
- High-resolution mass spectrometry-based non-targeted analysis.
- In-vivo 18O labeling and MALDI-tandem MS imaging.
Main Results:
- Detection of 70 distinct oxPCs in mice with acute liver failure.
- Identification of doubly oxygenated polyunsaturated fatty acid-PCs (PC PUFA;O2) in early liver injury.
- Localization of PC PUFA;O2 within hepatocytes expressing CYP2E1 and depleted of glutathione.
Conclusions:
- Doubly oxygenated PUFA-PCs are early markers of liver injury.
- Specific hepatocyte populations are key sites for PC PUFA;O2 production and accumulation.
- The developed methods advance the study of lipid peroxidation in disease pathogenesis.
