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

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Robert H. Rice

PROVIDER: MSV000090901 | MassIVE | Wed Dec 14 10:35:00 GMT 2022

SECONDARY ACCESSION(S): PXD038827

REPOSITORIES: MassIVE

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

Lin Lo-Wei LW Durbin-Johnson Blythe P BP Rocke David M DM Salemi Michelle M Phinney Brett S BS Rice Robert H RH

Toxicological sciences : an official journal of the Society of Toxicology 20231201 1

Cornified envelopes (CEs) of human epidermis ordinarily consist of transglutaminase-mediated cross-linked proteins and are essential for skin barrier function. However, in addition to enzyme-mediated isopeptide bonding, protein cross-linking could also arise from oxidative damage. Our group recently demonstrated abnormal incorporation of cellular proteins into CEs by pro-oxidants in woodsmoke. In this study, we focused on 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), mesquite liquid smoke (MLS), and ...[more]

PMID: 37788135

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