title: Proteomic analysis of human keratinocyte response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure.
abstract: Chronic exposure to 2,3,7,8-tetrachlorodibeno-p-dioxin (TCDD) and related polyhalogenated organic pollutants occurs as a consequence of modern life. Exploring the cellular basis for their action is anticipated to help understand the risk they pose and improve the foundation for their regulation. A basis for the striking change in human keratinocyte colony morphology due to TCDD exposure has been investigated by shotgun proteomics. Concentrating on changes in protein levels among three cell strains has revealed significant decreases in the differentiation markers filaggrin, keratin 1, and keratin 10. EGF treatment in concert with TCDD enhanced the changes in these markers and several other proteins while reducing the levels of certain other proteins. The only protein stimulated by TCDD in all three strains and reversed by EGF in them was vimentin, not previously observed to be in the aryl hydrocarbon receptor response domain. Although TCDD is often proposed to enhance keratinocyte differentiation, proteomic analysis reveals it uncouples the differentiation program and suggests that reduced levels of differentiation marker proteins contribute to the observed excessive stratification it induces.
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , Beijing 100085, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Hu
authors.forename: Robert H
authors.initials: RH
authors.lastname: Rice
authors.forename: Qin
authors.initials: Q
authors.lastname: Qin
authors.forename: Brett S
authors.initials: BS
authors.lastname: Phinney
authors.forename: Richard A
authors.initials: RA
authors.lastname: Eigenheer
authors.forename: Wenjun
authors.initials: W
authors.lastname: Bao
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
mesh_terms: D000704:Analysis of Variance; D002460:Cell Line; D004785:Environmental Pollutants / Q000633:toxicity*; D000091344:Filaggrin Proteins; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D053556:Keratin-1 / Q000378:metabolism; D053550:Keratin-10 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism*; D013058:Mass Spectrometry; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D040901:Proteomics / Q000379:methods*; D014746:Vimentin
chemical_list: D004785:Environmental Pollutants; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D053556:Keratin-1; D000072317:Polychlorinated Dibenzodioxins; D014746:Vimentin; D053550:Keratin-10