Site‐specific identification and validation of hepatic histone nitration in vivo: Implications for alcohol‐induced liver injury
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Le résumé fourni par la source
Oxidative and nitrative stress have been implicated in the molecular mechanisms underlying a variety of biological processes and disease states including cancer, aging, cardiovascular disease, neurological disorders, diabetes, and alcohol-induced liver injury. One marker of nitrative stress is the formation of 3-nitrotyrosine, or protein tyrosine nitration (PTN), which has been observed during inflammation and tissue injury; however, the role of PTN in the progression or possibly the pathogenesis of disease is still unclear. We show in a model of alcohol-induced liver injury that an increase in PTN occurs in hepatocyte nuclei within the liver of wild-type male C57BL/6J mice following chronic ethanol exposure (28 days). High-resolution mass spectrometric analysis of isolated hepatic nuclei revealed several novel sites of tyrosine nitration on histone proteins. Histone nitration sites were validated by tandem mass spectrometry (MS/MS) analysis of representative synthetic nitropeptides equivalent in sequence to the respective nitrotyrosine sites identified in vivo. We further investigated the potential structural impact of the novel histone H3 Tyr41 (H3Y41) nitration site identified using molecular dynamics (MD) simulations. MD simulations of the nitrated and non-nitrated forms of histone H3Y41 showed significant structural changes at the DNA interface upon H3Y41 nitration. The results from this study suggest that, in addition to other known post-translational modifications that occur on histone proteins (e.g., acetylation and methylation), PTN could induce chromatin structural changes, possibly affecting gene transcription processes associated with the development of alcohol-induced liver injury.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Site‐specific identification and validation of hepatic histone nitration in vivo: Implications for alcohol‐induced liver injury
- Date Crossref
- 03/05/2021
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Houston Methodist Department of Cardiovascular Regeneration pays non établi dans la noticeÉtablissement de santé
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University of South Florida Department of Cell Biology pays non établi dans la noticeUniversité ou école supérieure
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Albany College of Pharmacy and Health Sciences Department of Pharmaceutical Sciences pays non établi dans la noticeUniversité ou école supérieure
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Vanderbilt University MSRC Proteomics Core Laboratory pays non établi dans la noticeUniversité ou école supérieure
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Vanderbilt University Medical Center pays non établi dans la noticeÉtablissement de santé
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Moffitt Cancer Center Department of Tumor Biology pays non établi dans la noticeÉtablissement de santé
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Cincinnati Children's Hospital Medical Center Division of Experimental Hematology and Cancer Biology pays non établi dans la noticeÉtablissement de santé
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Research Institute 12902 Magnolia Drive Department of Tumor Biology H. Lee Moffitt Cancer Center & pays non établi dans la noticeStructure de recherche
Department of Cardiovascular Regeneration — Houston Methodist, Department of Cell Biology — University of South Florida et Department of Pharmaceutical Sciences — Albany College of Pharmacy and Health Sciences, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.