Mass spectrometric identification of isocyanate-induced modifications of keratins in human skin

Albert G. Hulst, Daan R W Verstappen, Debora Van Der Riet - Van Oeveren, Nico P E Vermeulen, Daan Noort*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

In the current paper we show that exposure of human callus to isocyanates leads to covalent modifications within keratin proteins. Mass spectrometric analyses of pronase digests of keratin isolated from exposed callus show that both mono- and di-adducts (for di-isocyanates) are predominantly formed on the ε-amino group of lysine. In addition, numerous modified tryptic keratin fragments were identified, demonstrating rather random lysine modification. Interestingly, preliminary experiments demonstrate that in case of MDI a similar lysine di-adduct was formed with lung elastin. Our data support the hypothesis that skin sensitization through antigenic modifications of skin proteins by isocyanates could play a role in occupational isocyanate-induced asthma. It is further envisaged that the elucidated adducts will also have great potential for use as biomarkers to assess skin exposure to isocyanates. Advantageously, the various lysine adducts display the presence of a characteristic daughter fragment at m/z 173.1 [lysine-NCO]+, enabling generic and rapid screening for exposure to isocyanates.

Original languageEnglish
Pages (from-to)141-150
Number of pages10
JournalChemico-Biological Interactions
Volume237
DOIs
Publication statusPublished - 22 Jun 2015

Keywords

  • Adducts
  • Biomarkers
  • Exposure assessment
  • Isocyanates
  • Keratin
  • Skin

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