Marie-Caroline Smith
Laboratoire Universitaire de Biodiversité et Ecologie Microbienne, France
Title: Early proteomic changes induced by fusariotoxin single and combined exposures on human hepatocytes
Biography
Biography: Marie-Caroline Smith
Abstract
While the reality of mycotoxin co-contamination of food commodities is now well-established, the assessment of the toxicological impact of mycotoxin mixtures is still rare. Moreover, studies concerning the mechanistic cellular response to mycotoxins (alone or in mixture) are lacking. Among the infinite number of possible mycotoxin mixtures found, combinations of toxins from Fusarium spp. (called fusariotoxins) are particularly widespread in the North temperate zone of the world and therefore of interest. In this context, our main objective was to compare the cellular mechanisms involved in response to single and combined exposures of the human hepatocyte cell line HepaRG to two relevant fusariotoxins, deoxynivalenol and zearalenone. After 1 h of exposure with deoxynivalenol and/or zearalenone at low cytotoxic doses (IC10), proteomes of HepaRG cells were analyzed by LC-MS/MS and compared to the control condition without mycotoxin. Among the 3000 identified proteins per sample, 55 showed a significant enhanced or reduced abundance compared to the non-exposed cells. Interestingly, none of these 55 proteins were in common between the cells exposed to deoxynivalenol and those exposed to zearalenone. Noteworthy, very few proteins were common between the mixture and the toxins alone. Cells exposed to deoxynivalenol showed an increased expression of proteins involved in DNA topological changes, chromosome segregation and proteolysis, whereas zearalenone mainly induced changes for proteins involved in response to steroid hormone stimulus. Concerning the mixture, the main affected biological processes were, among others, cell cycle phase, DNA packaging and cell division. Thus, these results highlighted different cellular pathways responded to different single and combined mycotoxins exposures.