Treatment of keratin intermediate filaments with sulfur mustard analogs

John F. Hess, Paul G FitzGerald

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Sulfur mustard (SM) is an alkylating agent with a history of use as a chemical weapon. The chemical reactivity of sulfur mustard toward both proteins and nucleic acids coupled with the hours long delay between exposure and appearance of blisters has prevented the determination of the mechanism of blister formation. We have treated assembled keratin intermediate filaments with analogs of sulfur mustard to simulate exposure to SM. We find that treatment of intact filaments with chloroethyl ethyl sulfide (CEES) or mechlorethamine (MEC) produces aggregates of keratin filaments with little native appearing structure. Treatment of a mix of epidermal keratins 1/10 (keratin pair 1 and 10) and keratins 5/14 with a sulfhydryl-specific modification reagent also results in filament abnormalities. Our results are consistent with the hypothesis that modification of keratins by SM would result in keratin filament destruction, leading to lysis of epidermal basal cells and skin blistering.

Original languageEnglish (US)
Pages (from-to)616-621
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume359
Issue number3
DOIs
StatePublished - Aug 3 2007

Keywords

  • Intermediate filament
  • Keratin
  • Keratin intermediate filament
  • kIF
  • Mustard gas
  • Skin blistering
  • Sulfur mustard

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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