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

Free Radic Biol Med. 2024 Apr 23:S0891-5849(24)00409-X. doi: 10.1016/j.freeradbiomed.2024.04.230. Online ahead of print.ABSTRACTAt 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/H2O2 with increasing I⁻. Incubation of BSA with MPO/H2O2/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 dimeriz...

Source: Free Radical Biology and Medicine - April 25, 2024 Category: Biology Authors: Kathrine V Jokumsen Valerie H Huhle Per M H ägglund Michael J Davies Luke F Gamon Source Type: research