Bromofatty aldehyde derived from bromine exposure and myeloperoxidase and eosinophil peroxidase modify GSH and protein

Mark A. Duerr, Elisa N.D. Palladino, Celine L. Hartman, James A. Lambert, Jacob D. Franke, Carolyn J. Albert, Sadis Matalon, Rakesh P. Patel, Arne Slungaard, David A. Ford

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9 Scopus citations

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 -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 Br 2 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.

Original languageEnglish (US)
Pages (from-to)696-705
Number of pages10
JournalJournal of lipid research
Volume59
Issue number4
DOIs
StatePublished - 2018

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health Grant R01GM115552 (D.A.F.) and National Institute of Environmental Health Sciences Grants U01ES023759 (R.P.P), U01ES026458 (S.M.), and U01ES027697 (S.M.). Additional support was provided through subcontracts to D.A.F. from National Institute of Environmental Health Sciences Grants U01ES023759, U01ES026458, and U01ES027697. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Manuscript received 4 January 2018 and in revised form 9 February 2018. Published, JLR Papers in Press, February 14, 2018 DOI https://doi.org/10.1194/jlr.M083279

Keywords

  • Fatty aldehydes
  • Glutathione
  • Hypobromous acid
  • Hypochlorous acid
  • Plasmalogen
  • Thiols

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