Abstract：
:The α,β-unsaturated aldehyde 4-hydroxynonenal (HNE) is formed through lipid peroxidation during oxidative stress. As a highly reactive electrophile, it is able to form adducts with various biomolecules, including proteins. These protein modifications could modulate many signaling pathways, as well as cell differentiation and proliferation, and thus could be highly important in the context of the extracellular matrix and degradation of articular cartilage. This study specifically investigated the role of HNE as a bioactive molecule in chondrocytes of osteoarthritis (OA) patients. Chondrocyte extracts of OA and non-OA patients were analyzed for HNE binding using Western blot and bottom-up LC-MS/MS analyses. HNE-modified histones, H2A and H2B, and histone deacetylase were identified using anti-HNE antibodies. Furthermore, peptide sequencing and database searching revealed 95 distinct HNE-modified proteins and their exact modification sites, with 88 protein adducts being unique to OA chondrocytes. HNE-proteins of specific interest included histone H2A, H2B and H4, collagen alpha-3(VI) chain, eukaryotic initiation factor 4A-I, and nucleolar RNA helicase 2. Comparing their MS/MS spectra to those of HNE-modified standard peptides further validated the six HNE-proteins. SIGNIFICANCE: HNE binding to proteins has been shown to result in multiple abnormalities of chondrocyte phenotype and function, suggesting its contribution in OA development. Considering the increased levels of HNE in OA cartilage, this reactive aldehyde could play a role in OA. This work represents a clinically-relevant in vivo study to demonstrate the pathophysiological role of HNE in human OA. Since HNE binding can alter protein conformation and function, it remains highly relevant to study the effects of this modification in OA.
journal_name
J Proteomicsjournal_title
Journal of proteomicsauthors
Geib T,Iacob C,Jribi R,Fernandes J,Benderdour M,Sleno Ldoi
10.1016/j.jprot.2020.104024subject
Has Abstractpub_date
2021-02-10 00:00:00pages
104024eissn
1874-3919issn
1876-7737pii
S1874-3919(20)30392-4journal_volume
232pub_type
杂志文章abstract：UNLABELLED:Dilated cardiomyopathy (DCM) is a severe heart disease characterized by progressive ventricular dilation and impaired systolic function of the left ventricle. We recently identified a novel pathogenic mutation in the LMNA gene in a family affected by DCM showing sudden death background. We now aimed to ident...
journal_title：Journal of proteomics
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journal_title：Journal of proteomics
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journal_title：Journal of proteomics
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journal_title：Journal of proteomics
pub_type： 杂志文章,评审
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pub_type： 杂志文章
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journal_title：Journal of proteomics
pub_type： 杂志文章
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journal_title：Journal of proteomics
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