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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
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Edité par CCSD ; Wiley-VCH Verlag -
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… Despite its inhibitory effect on de novo ceramide synthesis, its molecular mechanism of action and toxicity are not totally elucidated. To explore the mechanism of FB1 toxicity, we analyzed the transcriptome and kinome of two organs targeted by FB1: the liver and the jejunum. Pigs were fed for 4 weeks on 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. 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 Fumonin B1 which are on of the most spread nutritional's contaminant in the world. This article is protected by copyright. All rights reserved.
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