ArticleProceedings of the National Academy of Sciences of the United States of America2006
Bispecific abs against modified protein and DNA with oxidized lipids.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 31 citations in OpenAlex.
- Review
- Oxidative stress products and managements in atopic dermatitis.Frontiers in medicine · 2025Review
- DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity.AIMS genetics · 2017Review
- Significance of Lipid-Derived Reactive Aldehyde-Specific Immune Complexes in Systemic Lupus Erythematosus.PloS one · 2016Article
- Detection of electrophile-sensitive proteins.Biochimica et biophysica acta · 2014Review
- Multiple sclerosis: molecular mechanisms and therapeutic opportunities.Antioxidants & redox signaling · 2013Review
- Interaction of aldehydes derived from lipid peroxidation and membrane proteins.Frontiers in physiology · 2013Review
- The lipid peroxidation product 4-hydroxy-2-nonenal: Advances in chemistry and analysis.Redox biology · 2013Review
- Structural analysis of a protective epitope of the Francisella tularensis O-polysaccharide.Biochemistry · 2012Article
- Oxidative stress-induced antibodies to carbonyl-modified protein correlate with severity of chronic obstructive pulmonary disease.American journal of respiratory and critical care medicine · 2011Article
- Covalent binding antibodies suppress advanced glycation: on the innate tier of adaptive immunity.Acta naturae · 2009Article
- Elevated oxidative stress in erythrocytes due to a SOD1 deficiency causes anaemia and triggers autoantibody production.The Biochemical journal · 2007Article
- Crystallization and molecular-replacement studies of the monoclonal antibody mAbR310 specific for the (R)-HNE-modified protein.Acta crystallographica. Section F, Structural biology and crystallization communications · 2006Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
4-Hydroxy-2-nonenal (HNE), a racemic mixture of 4R- and 4S-enantiomers, is a major product of lipid peroxidation and is believed to be largely responsible for the cytopathological effects observed during oxidative stress. HNE reacts with histidine to form a stable HNE-histidine Michael addition-type adduct possessing three chiral centers in the cyclic hemiacetal structure. We have previously raised the mAbs, anti-R mAb 310 and anti-S mAb S412, that enantioselectively recognized the R-HNE-histidine and R-HNE-histidine adducts, respectively, and demonstrated the presence of both epitopes in vivo. In the present study, to further investigate the anti-HNE immune response, we analyzed the variable genes and primary structure of these Abs and found that the sequence of R310 was highly homologous to anti-DNA autoantibodies, the hallmark of systemic lupus erythematosus. An x-ray crystallographic analysis of the R310 Fab fragment showed that the R-HNE-histidine adduct binds to a hydrophobic pocket in the antigen-binding site. Despite the structural identity to the anti-DNA autoantibodies, however, R310 showed only a slight crossreactivity with the native double-stranded DNA, whereas the Ab immunoreactivity was dramatically enhanced by the treatment of the DNA with 4-oxo-2-nonenal (ONE), an analog of HNE. Moreover, the 7-(2-oxo-heptyl)-substituted 1,N2-etheno-type ONE-2'-deoxynucleoside adducts were identified as alternative epitopes of R310. Molecular mimicry between the R-HNE-histidine configurational isomers and the ONE-DNA base adducts is proposed for the dual crossreactivity.
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