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

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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).", "claims": [{"id": "claim-target-result", "statement": "The study’s headline was that acute naphthalene exposure dramatically reduced airway Cyp2f2 and secretoglobin 1A1, while tolerance upregulated heat shock proteins and protein disulfide isomerases; protein identifications used a 3% false discovery rate, and source data were deposited in PRIDE project PRD000846 (experiments 30584 and 30585).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:25825134", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Cyp2f2 and secretoglobin 1A1 are decreased dramatically in airways of mice exposed for 4 hrs, a finding consistent with the fact that P450’s are localized primarily in Clara cells."}, {"asset": "source:pmid:25825134", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "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."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The study’s headline was that acute naphthalene exposure dramatically reduced airway Cyp2f2 and secretoglobin 1A1, while tolerance upregulated heat shock proteins and protein disulfide isomerases; protein identifications used a 3% false discovery rate, and source data were deposited in PRIDE project PRD000846 (experiments 30584 and 30585).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:25825134"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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