title: Alterations in the proteome of the respiratory tract in response to single and multiple exposures to naphthalene.
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).
authors.affiliation: Department of Animal Science, College of Agricultural and Environmental Sciences, University of California, Davis, CA, USA.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Kültz
authors.affiliation: Department of Animal Science, College of Agricultural and Environmental Sciences, University of California, Davis, CA, USA.
authors.forename: Johnathon
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Animal Science, College of Agricultural and Environmental Sciences, University of California, Davis, CA, USA.
authors.forename: Romina
authors.initials: R
authors.lastname: Sacchi
authors.affiliation: Depatment of Molecular Biosciences, University of California, Davis, CA, USA.
authors.forename: Dexter
authors.initials: D
authors.lastname: Morin
authors.affiliation: Depatment of Molecular Biosciences, University of California, Davis, CA, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Buckpitt
authors.affiliation: Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Van Winkle
mesh_terms: D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002853:Chromatography, Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D009281:Naphthalenes / Q000494:pharmacology*; D009831:Olfactory Mucosa / Q000166:cytology / Q000378:metabolism; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation / Q000187:drug effects; D014598:Uteroglobin / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; D009281:Naphthalenes; D020543:Proteome; C556390:Scgb1a1 protein, mouse; C031721:naphthalene; D003577:Cytochrome P-450 Enzyme System; D014598:Uteroglobin; C110333:Cyp2f2 protein, mouse; D019704:Protein Disulfide-Isomerases
keywords: Animal proteomics; Clara cells; Metabolic activation; Naphthalene; Protein adduct
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