Formation of Nɛ-(succinyl)lysine in vivo: a novel marker for docosahexaenoic acid-derived protein modification
Open accessAbstract
Free radical-catalyzed peroxidation of docosahexaenoic acid (DHA, C22:6/omega-3) generates various lipid peroxidation products that covalently modify biomolecules such as proteins. Under a free radical-generating system, DHA significantly modified lysine residues in bovine serum albumin. Upon incubation of oxidized DHA with an amino-compound pyridoxamine or a lysine-containing peptide, N-propanoyl and N-succinyl adducts were determined to be the major modification products. The hydroperoxide levels in the oxidized DHA closely reflected the formation of the N(epsilon)-(succinyl)lysine (SUL) upon reaction with the peptide, indicating that the hydroperoxides of DHA represent a potential pathway for the formation of SUL. To detect the DHA-derived protein modification in vivo, we developed a monoclonal antibody (mAb2B12) specific to SUL and found that the antibody specifically reacts with the SUL moiety. The formation of SUL was then immunochemically demonstrated in the liver of mice fed with DHA followed by intraperitoneal injection of carbon tetrachloride (CCl(4)), a hepatic lipid peroxidation model. Immunoreactive materials with mAb2B12 were observed in the DHA + CCl(4) group, but were not significant in the control, DHA-alone, and CCl(4)-alone groups. These data suggest that the formation of DHA-derived adducts such as SUL may be implicated in the oxidative damage observed in DHA-enriched tissues.
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Earlier work did not conclusively determine the chemical structure of the lysine modification.
“However, these studies were not sufficient to fully establish the chemical structure of the modification.”
From SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways (2013) · cites this paper as Kawai et al., 2006
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- Authors
- Kawai, Y., Fujii, H., Okada, M., Tsuchie, Y., Uchida, K., & Osawa, T.
- Affiliations
- Nagoya University (JP)
- Corresponding author
- Kawai, Yoshichika
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2006-07
- Volume
- 47
- Issue
- 7
- Pages
- 1386-1398
- ISSN
- 0022-2275 (ISSN-L)
- OpenAlex
- W2156086508
- Cited by
- 53
- References
- 50
- Citations by year
- 2025: 3 · 2024: 1 · 2022: 2 · 2021: 5 · 2020: 3 · 2018: 3 · 2017: 2 · 2016: 1 · 2014: 1 · 2013: 10 · 2012: 3
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- docosahexaenoic acid, lipid peroxidation, protein modification, lysine adducts, hydroperoxides, monoclonal antibodies, carbon tetrachloride, hepatic lipid peroxidation, oxidative damage, omega-3 fatty acids, bovine serum albumin
- MeSH terms
- Animals, Antibodies, Monoclonal, Docosahexaenoic Acids, Immunohistochemistry, Liver, Lysine, Male, Mice, Inbred ICR, Protein Processing, Post-Translational, Proteins, Succinates, Lipid Peroxidation, Biomarkers, Mice, In Vitro Techniques
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