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Oxidized Phosphatidylcholines That Modify Proteins
Open accessAbstract
Oxidatively modified low density lipoprotein (OxLDL) is known to be involved in atherogenesis. We have previously developed a murine monoclonal antibody, FOH1a/DLH3, which recognized oxidatively modified lipoproteins as well as foam cells in human atherosclerotic lesions (Itabe, H., Takeshima, E., Iwasaki, H., Kimura, J., Yoshida, Y., Imanaka, T., and Takano, T. (1994) J. Biol. Chem. 269, 15274-15279). The antigen of this monoclonal antibody was formed by peroxidation of phosphatidylcholine (PC), and the antigenic oxidized PC (OxPC) derivatives are thought to form complexes with polypeptides including apolipoproteins. OxLDL was measured by a sensitive sandwich enzyme-linked immunosorbent assay using the monoclonal antibody and anti-human apolipoprotein B antibody, in which antigenic OxPC competed with OxLDL. When antigenic activities of PC analogs were tested by the competition assay, 1-palmitoyl-2-(9-oxononanoyl) PC (9-CHO PC) and the hydroperoxide of egg PC potently inhibited the detection of OxLDL. 1-Palmitoyl-2-linoleoyl PC was oxidized with ferrous ion and ascorbic acid, and the antigenic products were purified from the OxPC extracts on high pressure liquid chromatography columns and subsequently analyzed by laser desorption mass spectrometry. Molecular weight determination and retention times of high pressure liquid chromatography suggest that one of these products was 9-CHO PC. Other products are thought to be 8-carbon aldehyde, dihydroxy, and ketohydroxy derivatives of PC. When a C-terminal 16-mer synthetic peptide of the 70-kDa peroxisomal membrane protein was simply incubated with 9-CHO PC, it was found to be reactive in a sandwich enzyme-linked immunosorbent assay using FOH1a/DLH3 and an anti-peptide antiserum. These results suggest that the anti-OxLDL monoclonal antibody FOH1a/DLH3 reacts with several oxidized products of PC including aldehyde derivatives of PC, which covalently modify polypeptides.
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“From the viewpoint of cell biology672, 673), immunohistology674, 675) and other factors, it has become clear that LDL oxidation is an important aspect of the pathogenic mechanism of atherosclerosis.”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [673]
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Metadata
- Authors
- Itabe, H., Yamamoto, H., Suzuki, M., Kawai, Y., Nakagawa, Y., Suzuki, A., Imanaka, T., & Takano, T.
- Affiliations
- Teikyo University (JP)
- Tokyo Metropolitan Institute of Medical Science (JP)
- Kitasato University (JP)
- Corresponding author
- Itabe, Hiroyuki
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1996-12
- Volume
- 271
- Issue
- 52
- Pages
- 33208-33217
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1994240931
- Cited by
- 128
- References
- 44
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 2 · 2020: 4 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 2 · 2014: 7 · 2013: 2 · 2012: 1
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Kanazawa University
- Japan Society for the Promotion of Science (06454602)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- oxidized phosphatidylcholine, oxidized LDL, atherosclerosis, peroxidation, aldehyde derivatives, protein modification, apolipoprotein B, peroxisomal membrane proteins, foam cells, lipoprotein oxidation
- MeSH terms
- Animals, Antibodies, Monoclonal, Chromatography, High Pressure Liquid, Cricetinae, Humans, Lipoproteins, LDL, Molecular Weight, Magnetic Resonance Spectroscopy, Oxidation-Reduction, Phosphatidylcholines, Proteins, CHO Cells
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