Deoxynivalenol and human epidermal cells: proteomic profiling indicates alterations of cell membrane integrity and barrier function - phosphoproteomics

ABSTRACT: The possibility to combine untargeted proteomic workflows to more classical experimental approaches is continuously opening new insights in all branches of biological sciences. Deoxynivalenol (vomitoxin, DON) is a secondary metabolite produced by Fusarium spp. fungi and it is one of the most recurrent mycotoxins worldwide. DON is known to inhibit protein synthesis and as such to interact with the different cell types in multiple and complex ways. For the purpose of this study epidermoid squamous cell carcinoma cells A431 and primary human HEKn cells were incubated with DON for 24 h and toxin dependent alteration of the proteome profile was observed in nuclear and cytoplasmic fractions. In A431 cells, DON significantly down-regulated ribosomal proteins, as well as mitochondrial respiratory chain elements (OXPHOS regulation) and transport proteins (TOMM22; TOMM40; TOMM70A). In line with the impairment of the mitochondrial function, altered metabolic capability was indicated, with particular target of the lipid synthesis machinery. Functional effect of the mycotoxin on cell membranes was confirmed by live cell imaging and by membrane fluidity assay. Downregulation of the squalene synthase (FDFT1) was consistent in both cell types and the effects of the toxin on cell membranes and cholestherol biosyhtesis were found as common denominator for both A431 and HEKn. Overall we described crucial molecular events pointing toward the capability of DON to impair skin barrier function. Data generated in the study are fully accessible via ProemeXchange with the accession numbers PXD011474 and PXD013613.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epidermal Cell

DISEASE(S): Squamous Cell Carcinoma

SUBMITTER: Christopher Gerner  

LAB HEAD: Christopher Gerner

PROVIDER: PXD016153 | Pride | 2021-06-01

REPOSITORIES: Pride