Title: Bromofatty aldehyde derived from bromine exposure and myeloperoxidase and eosinophil peroxidase modify GSH and protein.
Authors: Duerr, Mark A; Palladino, Elisa N D; Hartman, Celine L; Lambert, James A; Franke, Jacob D; Albert, Carolyn J; Matalon, Sadis; Patel, Rakesh P; Slungaard, Arne; Ford, David A
Published In J Lipid Res, (2018 04)
Abstract: α-Chlorofatty aldehydes (α-ClFALDs) and α-bromofatty aldehydes (α-BrFALDs) are produced in activated neutrophils and eosinophils. This study investigated the ability of α-BrFALD and α-ClFALD to react with the thiols of GSH and protein cysteinyl residues. Initial studies showed that 2-bromohexadecanal (2-BrHDA) and 2-chlorohexadecanal (2-ClHDA) react with GSH producing the same fatty aldehyde-GSH adduct (FALD-GSH). In both synthetic and cellular reactions, FALD-GSH production was more robust with 2-BrHDA compared with 2-ClHDA as precursor. NaBr-supplemented phorbol myristate acetate (PMA)-activated neutrophils formed more α-BrFALD and FALD-GSH compared with non-NaBr-supplemented neutrophils. Primary human eosinophils, which preferentially produce hypobromous acid and α-BrFALD, accumulated FALD-GSH following PMA stimulation. Mice exposed to Br2 gas had increased levels of both α-BrFALD and FALD-GSH in the lungs, as well as elevated systemic plasma levels of FALD-GSH in comparison to mice exposed to air. Similar relative reactivity of α-ClFALD and α-BrFALD with protein thiols was shown using click analogs of these aldehydes. Collectively, these data demonstrate that GSH and protein adduct formation are much greater as a result of nucleophilic attack of cysteinyl residues on α-BrFALD compared with α-ClFALD, which was observed in both primary leukocytes and in mice exposed to bromine gas.
PubMed ID: 29444934
MeSH Terms: Aldehydes/blood*; Animals; Bromine/administration & dosage; Bromine/blood*; Click Chemistry; Eosinophil Peroxidase/blood*; Eosinophil Peroxidase/metabolism; Glutathione Transferase/blood*; Glutathione Transferase/metabolism; Healthy Volunteers; Humans; Mice; Peroxidase/blood*; Peroxidase/metabolism; RAW 264.7 Cells