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Identification of Signaling Pathways Targeted by the Food Contaminant FB1: Transcriptome and Kinome Analysis of Samples from Pig Liver and Intestine
Author(s) -
Régnier Marion,
Gourbeyre Pascal,
Pinton Philippe,
Napper Scott,
Laffite Joëlle,
Cossalter AnneMarie,
Bailly JeanDenis,
Lippi Yannick,
BertrandMichel Justine,
Bracarense Ana Paula F.R.L.,
Guillou Hervé,
Loiseau Nicolas,
Oswald Isabelle P.
Publication year - 2017
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.201700433
Subject(s) - kinome , fumonisin b1 , biology , transcriptome , pi3k/akt/mtor pathway , protein phosphatase 2 , protein kinase b , pten , tensin , signal transduction , sphingosine , phosphatase , biochemistry , phosphorylation , mycotoxin , gene expression , receptor , gene , food science
Scope Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium species. In mammals, this toxin causes widespread organ‐specific damage; it promotes hepatotoxicity, is immunotoxic, alters intestinal functions etc. Despite its inhibitory effect on de novo ceramide synthesis, its molecular mechanism of action and toxicity is not totally elucidated. Methods and results To explore the mechanism of FB1 toxicity, we analyzed the transcriptome and the kinome of two organs targeted by FB1: the liver and the jejunum. Pigs were fed for 4 weeks a control diet or a FB1‐contaminated diet (10 mg/kg). As expected, FB1‐exposed pigs gained less weight and displayed a higher sphinganine/sphingosine ratio. Comparison of the transcriptomes and the kinomes of treated versus control pigs showed striking differences. Among the disrupted pathways in liver and jejunum, we highlight Protein Kinase B (AKT) / Phosphatase and tensin homolog (PTEN) at the intersection of the FB1‐modulated pathways. Conclusion Most of the effects of FB1 are mediated by the regulation of ceramide level, which influences protein phosphatase 2 (PP2A) and the phosphoinositide 3‐kinase (PI3K)/AKT signaling pathway. This pathway might be a new target to counteract toxic effect of Fumonisin B1, which is one of the most spread food contaminant in the world.