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Potential of deoxynivalenol to induce transcription factors in human hepatoma cells
Author(s) -
Nielsen Carina,
Lippke Harald,
Didier Andrea,
Dietrich Richard,
Märtlbauer Erwin
Publication year - 2009
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200800475
Subject(s) - biology , transcription (linguistics) , activating transcription factor , transcription factor , gene expression , microbiology and biotechnology , gene , u937 cell , cell culture , hep g2 , egr1 , genetics , philosophy , linguistics
To assess the hepatotoxicity of deoxynivalenol (DON), human hepatoma cells (Hep‐G2) were used as an in vitro model. After exposing Hep‐G2 cells to low (1 μM) and high dose (10 μM), gene expression profiles were analysed by microarray. More than 5% of genes were up‐regulated, most of them being involved in transcriptional regulation. By real‐time RT‐PCR, elevated expression of transcription factors, commonly induced by activation of MAPK‐pathway, was demonstrated for Hep‐G2 cells on mRNA and protein level. Further studies, involving U937 human monocytes, showed that effects of DON treatment on mRNA and protein level were concentration‐dependent and cell‐specific. An inverse relation was noticed for the level of DON induced expression of transcription factors (JUN, FOS, EGR1 and ATF3) and the susceptibility of the cell lines towards the mycotoxin. This is the first report giving evidence that on a molecular level the mild hepatotoxic effects of DON are probably caused by the induction of transcription factors which are known to be associated with injury‐induced liver regeneration processes. With ATF3, a novel downstream target gene was identified in DON‐related cell signalling suggesting a potential linkage between molecular action and biological effects like reduction of glycogen storage in liver tissue.