Alterations in the proteome of the respiratory tract in response to single and multiple exposures to naphthalene

Dietmar Kültz, Johnathon Li, Romina Sacchi, Dexter Morin, Alan R Buckpitt, Laura Van Winkle

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Protein adduction is considered to be critical to the loss of cellular homeostasis associated with environmental chemicals undergoing metabolic activation. Despite considerable effort, our understanding of the key proteins mediating the pathologic consequences from protein modification by electrophiles is incomplete. This work focused on naphthalene (NA) induced acute injury of respiratory epithelial cells and tolerance which arises after multiple toxicant doses to define the initial cellular proteomic response and later protective actions related to tolerance. Airways and nasal olfactory epithelium from mice exposed to 15 ppm NA either for 4 h (acute) or for 4 h/day × 7 days (tolerant) were used for label-free protein quantitation by LC/MS/MS. Cytochrome P450 2F2 and secretoglobin 1A1 are decreased dramatically in airways of mice exposed for 4 h, a finding consistent with the fact that CYPs are localized primarily in Clara cells. A number of heat shock proteins and protein disulfide isomerases, which had previously been identified as adduct targets for reactive metabolites from several lung toxicants, were upregulated in airways but not olfactory epithelium of tolerant mice. Protein targets that are upregulated in tolerance may be key players in the pathophysiology associated with reactive metabolite protein adduction. All MS data have been deposited in the ProteomeXchange with identifier PXD000846 (http://proteomecentral.proteomexchange.org/dataset/PXD000846).

Original languageEnglish (US)
Pages (from-to)2655-2668
Number of pages14
JournalProteomics
Volume15
Issue number15
DOIs
StatePublished - Aug 1 2015

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Keywords

  • Animal proteomics
  • Clara cells
  • Metabolic activation
  • Naphthalene
  • Protein adduct

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

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