دورية أكاديمية
أعرض في EDS

Elevated levels of iodide promote peroxidase-mediated protein iodination and inhibit protein chlorination.

التفاصيل البيبلوغرافية
العنوان: Elevated levels of iodide promote peroxidase-mediated protein iodination and inhibit protein chlorination.
المؤلفون: Jokumsen KV; Dept. of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark., Huhle VH; Dept. of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany., Hägglund PM; Dept. of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark., Davies MJ; Dept. of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark., Gamon LF; Dept. of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: lgamon@sund.ku.dk.
المصدر: Free radical biology & medicine [Free Radic Biol Med] 2024 Aug 01; Vol. 220, pp. 207-221. Date of Electronic Publication: 2024 Apr 23.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: United States NLM ID: 8709159 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4596 (Electronic) Linking ISSN: 08915849 NLM ISO Abbreviation: Free Radic Biol Med Subsets: MEDLINE
أسماء مطبوعة: Publication: Tarrytown, NY : Elsevier Science
Original Publication: New York : Pergamon, c1987-
مواضيع طبية MeSH: Peroxidase*/metabolism , Halogenation* , Iodides*/metabolism , Iodides*/chemistry , Lactoperoxidase*/metabolism , Lactoperoxidase*/chemistry , Hypochlorous Acid*/metabolism , Hydrogen Peroxide*/metabolism, Humans ; Oxidation-Reduction ; Iodine Compounds
مستخلص: At inflammatory sites, immune cells generate oxidants including H₂O₂. Myeloperoxidase (MPO), released by activated leukocytes employs H₂O₂ and halide/pseudohalides to form hypohalous acids that mediate pathogen killing. Hypochlorous acid (HOCl) is a major species formed. Excessive or misplaced HOCl formation damages host tissues with this linked to multiple inflammatory diseases. Previously (Redox Biology, 2020, 28, 101331) we reported that iodide (I⁻) modulates MPO-mediated protein damage by decreasing HOCl generation with concomitant hypoiodous acid (HOI) formation. HOI may however impact on protein structure, so in this study we examined whether and how HOI, from peroxidase/H₂O₂/I⁻ systems ± Cl⁻, modifies proteins. Experiments employed MPO and lactoperoxidase (LPO) and multiple proteins (serum albumins, anastellin), with both chemical (intact protein and peptide mass mapping, LC-MS) and structural (SDS-PAGE) changes assessed. LC-MS analyses revealed dose-dependent iodination of anastellin and albumins by LPO/H 2 O 2 with increasing I⁻. Incubation of BSA with MPO/H 2 O 2 /Cl⁻ revealed modest chlorination (Tyr286, Tyr475, ∼4 %) and Met modification. Lower levels of these species, and extensive iodination at specific Tyr and His residues (>20 % modification with ≥10 μM I⁻) were detected with increasing I⁻. Anastellin dimerization was inhibited by increasing I⁻, but less marked changes were observed with albumins. These data confirm that I⁻ competes with Cl⁻ for MPO and is an efficient HOCl scavenger. These processes decrease protein chlorination and oxidation, but result in extensive iodination. This is consistent with published data on the presence of iodinated Tyr on neutrophil proteins. The biological implications of protein iodination relative to chlorination require further clarification.
Competing Interests: Declaration of competing interest MJD declares consultancy contracts with Novo Nordisk A/S, and is a Director and major shareholder in the start-up company Seleno Therapeutics plc. These funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Prof. Michael Davies is also an Editorial Board Member for Free Radical Biology and Medicine but was not involved in the editorial review or the decision to publish this article.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: 3-Chlorotyrosine; 3-Iodotyrosine; Chlorination; Hypochlorous acid; Iodination; Methionine sulfoxide; Post-translational modifications; Protein oxidation; myeloperoxidase
المشرفين على المادة: EC 1.11.1.7 (Peroxidase)
0 (Iodides)
EC 1.11.1.- (Lactoperoxidase)
712K4CDC10 (Hypochlorous Acid)
BBX060AN9V (Hydrogen Peroxide)
2PYC923C5W (hypoiodous acid)
EC 1.11.1.7 (MPO protein, human)
0 (Iodine Compounds)
تواريخ الأحداث: Date Created: 20240425 Date Completed: 20240526 Latest Revision: 20240526
رمز التحديث: 20240527
DOI: 10.1016/j.freeradbiomed.2024.04.230
PMID: 38663830
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-4596
DOI:10.1016/j.freeradbiomed.2024.04.230