RESUMEN
Deoxynivalenol (vomitoxin, DON) is a secondary metabolite produced by Fusarium spp. fungi and it is one of the most prevalent mycotoxins worldwide. Crop infestation results not only in food and feed contamination, but also in direct dermal exposure, especially during harvest and food processing. To investigate the potential dermotoxicity of DON, epidermoid squamous cell carcinoma cells A431 were compared to primary human neonatal keratinocytes (HEKn) cells via proteome/phosphoproteome profiling. In A431 cells, 10 µM DON significantly down-regulated ribosomal proteins, as well as mitochondrial respiratory chain elements (OXPHOS regulation) and transport proteins (TOMM22; TOMM40; TOMM70A). Mitochondrial impairment was reflected in altered metabolic competence, apparently combined with interference of the lipid biosynthesis machinery. Functional effects on the cell membrane were confirmed by live cell imaging and membrane fluidity assays (0.1-10 µM DON). Moreover, a common denominator for both A431 and HEKn cells was a significant downregulation of the squalene synthase (FDFT1). In sum, proteome alterations could be traced back to the transcription factor Klf4, a crucial regulator of skin barrier function. Overall, these results describe decisive molecular events sustaining the capability of DON to impair skin barrier function. Proteome data generated in the study are fully accessible via ProteomeXchange with the accession numbers PXD011474 and PXD013613.
Asunto(s)
Células Epidérmicas/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Lípidos/biosíntesis , Tricotecenos/toxicidad , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Células Cultivadas , Relación Dosis-Respuesta a Droga , Células Epidérmicas/patología , Fusarium/metabolismo , Humanos , Queratinocitos/patología , Mitocondrias/efectos de los fármacos , Mitocondrias/patología , Proteómica , Metabolismo Secundario , Tricotecenos/administración & dosificación , Tricotecenos/aislamiento & purificaciónRESUMEN
Palytoxin (PLTX), one the most potent marine toxins, and/or its analogs, have been identified in different marine organisms, such as Palythoa soft corals, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria. Although the main concern for human health is PLTXs entrance in the human food chain, there is growing evidence of adverse effects associated with inhalational, cutaneous, and/or ocular exposure to aquarium soft corals contaminated by PLTXs or aquaria waters. Indeed, the number of case reports describing human poisonings after handling these cnidarians is continuously increasing. In general, the signs and symptoms involve mainly the respiratory (rhinorrhea and coughing), skeletomuscular (myalgia, weakness, spasms), cardiovascular (electrocardiogram alterations), gastrointestinal (nausea), and nervous (paresthesia, ataxia, tremors) systems or apparates. The widespread phenomenon, the entity of the signs and symptoms of poisoning and the lack of control in the trade of corals as aquaria decorative elements led to consider these poisonings an emerging sanitary problem. This review summarizes literature data on human poisonings due to, or ascribed to, PLTX-containing soft corals, focusing on the different PLTX congeners identified in these organisms and their toxic potential.