MassIVE MSV000090901

Partial Public PXD038827

Environmental pro-oxidants induce altered envelope protein profiles in human keratinocytes

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Description

Cornified envelopes (CEs) of human epidermis consist of transglutaminase-mediated cross-linked proteins and are essential for skin barrier function. Present work explores the influences of pro-oxidant pollutants on the CE protein profiles. In this study, we performed proteomic analysis on CEs induced by three types of environmental ROS generators, 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), mesquite liquid smoke (MLS), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), to evaluate the impacts of oxidative conditions on the CE proteome. Due to its non-adduct-forming property, DMNQ (a redox cycling compound) produced the fewest changes in CE proteins compared to control CEs (induced by ionophore-mediated membrane permeabilization). MLS is an extract of woodsmoke condensate and is rich in carbonyls. Likely altering the CE proteome through protein carbonylation, it stimulated incorporation of mitochondrial proteins as its main targets. Finally, TCDD altered the CE protein composition through changes in gene expression, especially those downstream of aryl hydrocarbon receptor signaling. Increased incorporation into CEs of chaperones and proteasomal proteins was found in all three treatments, indicating that even proteins functioning in protein quality control can become targets of oxidative stress. The accumulation of unwanted protein cross-links has been associated with aging and the progression of various human diseases. In the skin, oxidatively induced cross-linking could result in abnormal incorporation of cellular proteins into CEs, leading to altered CE composition and barrier dysfunction. Thus, this study helps elucidate the potential of environmental stressors to trigger disease onset. [doi:10.25345/C56Q1SN4Z] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: cornified envelope, covalent cross-link, oxidative stress, proteomics

Contact

Principal Investigators:
(in alphabetical order) 		Robert H. Rice, UC Davis, USA
Submitting User: brettsp1

Publications

Lin LW, Durbin-Johnson BP, Rocke DM, Salemi M, Phinney BS, Rice RH.
Environmental pro-oxidants induce altered envelope protein profiles in human keratinocytes.
Toxicol Sci. 2023 Dec 21;197(1):16-26.

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