{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:22:04Z","timestamp":1776273724140,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R01 GM-115553"],"award-info":[{"award-number":["R01 GM-115553"]}]},{"name":"National Institutes of Health","award":["R21 ES-031562"],"award-info":[{"award-number":["R21 ES-031562"]}]},{"name":"National Institutes of Health","award":["S10OD025246"],"award-info":[{"award-number":["S10OD025246"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Neutrophils are important cellular mediators of injury and repair in diseases including ischemic heart disease, atherosclerosis, and sepsis. Myeloperoxidase-derived (MPO)-oxidants released from neutrophils are potential mediators of endothelial injury in disease. MPO-derived HOCl attacks plasmalogen phospholipid to liberate 2-chlorofatty aldehyde (2-ClFALD). Both 2-ClFALD and its oxidation product, 2-chlorofatty acid (2-ClFA), are electrophilic lipids, and both probably react with proteins through several mechanisms. In the present study, we investigate protein modification specifically by 2-ClFALD under non-reducing conditions (e.g., without stabilizing Schiff base bonds), which likely reflects nucleophilic targeting of the electrophilic chlorinated carbon. Protein modification by the \u03c9-alkyne analog of 2-chlorohexadecanal (2-ClHDA), 2-ClHDyA, was compared to that with the \u03c9-alkyne analog of 2-chlorohexadecanoic acid (2-ClHA), 2-ClHyA, in multiple cell lines, which demonstrated 2-ClFALD preferentially modifies proteins compared to 2-ClFA. The 2-ClHDyA modified proteins from EA.hy926 cells and human lung microvascular endothelial cells analyzed by shotgun proteomics and over-representation analysis included adherens junction, cell adhesion molecule binding, and cell substrate junction enrichment categories. It is possible that proteins in these groups may have roles in previously described 2-ClFALD-elicited endothelial barrier dysfunction.<\/jats:p>","DOI":"10.3390\/antiox11050940","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T21:52:11Z","timestamp":1652219531000},"page":"940","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Endothelial Cell Protein Targeting by Myeloperoxidase-Derived 2-Chlorofatty Aldehyde"],"prefix":"10.3390","volume":"11","author":[{"given":"Shubha","family":"Shakya","sequence":"first","affiliation":[{"name":"Center for Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO 63104, USA"},{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger A.","family":"Herr","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO 63104, USA"},{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6445-7948","authenticated-orcid":false,"given":"Haley L.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO 63104, USA"},{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raphael A.","family":"Zoeller","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn J.","family":"Albert","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO 63104, USA"},{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Ford","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO 63104, USA"},{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3389\/fphys.2018.00113","article-title":"Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types?","volume":"9","author":"Rosales","year":"2018","journal-title":"Front. 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