6533b822fe1ef96bd127d81b

RESEARCH PRODUCT

Transcriptional study after Beauvericin and Enniatin B combined exposure in Jurkat T cells

Lara ManyesLaura EscriváGuillermina FontManuel Alonso-garrido

subject

Cell signalingTranscription GeneticBiologyMitochondrionToxicologyJurkat cellsJurkat Cells03 medical and health scienceschemistry.chemical_compound0404 agricultural biotechnologyDepsipeptidesGene expressionTranscriptional regulationHumansCytotoxicityGene030304 developmental biology0303 health sciences04 agricultural and veterinary sciencesGeneral Medicine040401 food scienceBeauvericinCell biologyGene Expression RegulationchemistryDrug Therapy CombinationTranscriptomeFood Science

description

Simultaneous mycotoxins toxicity is complex and non-predictable based on their individual toxicities. Beauvericin and Enniatins are emerging mycotoxins highly co-occurrent in food and feed, and their cytotoxicity has been reported in several human cell lines. RNA-seq studies of individual exposure in Jurkat cells demonstrated human genome perturbation mainly affecting mitochondrial pathways, however, both mycotoxins showed differences between their toxic responses. This study investigates the transcriptional effects of combined exposure to Beauvericin and Enniatin B (1:1) (0.1, 0.5, 1.5 μM; 24 h) in Jurkat cells by qPCR on 30 selected target genes (10 mitochondrial, 20 nuclear). Gene expression after combined and individual exposures were compared and functional data analysis (ToxPi) on the most relevant biological processes (cycle and apoptosis regulation; cholesterol metabolism and transport; cellular signaling transduction; cellular stress responses; immune regulation; protein metabolism; retinoic acid metabolism; transcription regulation) was applied to RNA-seq data from individual exposure (1.5, 3, 5 μM; 24 h; Jurkat cells). Transcriptional changes, especially at mitochondrial level, were observed after Beauvericin-Enniatin B co-exposure including down-regulation of antioxidant activity related genes. Different expression patterns between combined and individual exposures were identified. ToxPi analysis confirmed different dose-dependent relationship profiles between these two mycotoxins after individual exposure.

https://doi.org/10.1016/j.fct.2019.05.018