Alterations in the proteomes of HepG2 and IHKE cells inflicted by six selected mycotoxins

Abstract

Toxic fungal secondary metabolites, referred to as mycotoxins, emerge in moldy food and feed and constitute a potent but often underestimated health threat for humans and animals. They are structurally diverse and can cause diseases after dietary intake even in low concentrations. To elucidate cellular responses and identify cellular targets of mycotoxins, a bottom-up proteomics approach was used. We investigated the effects of the mycotoxins aflatoxin B₁, ochratoxin A, citrinin, deoxynivalenol, nivalenol and penitrem A on the human hepatoblastoma cell line HepG2 and of ochratoxin A and citrinin on the human kidney epithelial cell line IHKE. Incubations were carried out at sub-cytotoxic concentrations to monitor molecular effects before acute cell death mechanisms predominate. Through these experiments, we were able to detect specific cellular responses that point towards the mycotoxins’ mode of action. Besides very well-described mechanisms like the ribotoxicity of the trichothecenes, we observed not yet described effects on different cellular mechanisms. For instance, trichothecenes lowered the apolipoprotein abundance and aflatoxin B₁ affected proteins related to inflammation, ribogenesis and mitosis. Ochratoxin A and citrinin upregulated the minichromosomal maintenance complex and nucleotide synthesis in HepG2 and downregulated histones in IHKE. Penitrem A reduced enzyme levels of the sterol biosynthesis. These results will aid in the elucidation of the toxicodynamic properties of this highly relevant class of toxins.