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Article Dans Une Revue Archives of Toxicology Année : 2015

New insights into the organ-specific adverse effects of fumonisin B1

Nicolas Loiseau
Aude Dupuy
  • Fonction : Auteur
Mirindra Rakotonirainy
  • Fonction : Auteur
Jennifer Loy
  • Fonction : Auteur
Jean-Luc Viadere
  • Fonction : Auteur
  • PersonId : 1206584
Anne Marie Cossalter
  • Fonction : Auteur
  • PersonId : 1070726
Jean-Denis Bailly
Olivier Puel
Martine Kolf-Clauw
  • Fonction : Auteur
Justine Bertrand-Michel

Résumé

Fumonisin B1 (FB1) is a well-known inhibitor of de novo sphingolipid biosynthesis, due to its ability to inhibit Ceramide Synthases (CerS) activity. In mammals, this toxin triggers broad clinical symptoms with multi-organ dysfunction such as hepatotoxicity or pulmonary edema. The molecular mechanism of CerS inhibition by FB1 remains unknown. Due to the existence of six mammalian CerS isoforms with a tissue specific expression pattern, we postulated that the organ specific adverse effects of FB1 might be due to different CerS isoforms. The sphingolipid contents of lung and liver were compared in normal and FB1-exposed piglets (gavage with 1.5 mg FB1/kg body weight daily for 9 days). The effect of the toxin on each CerS was deduced from the analysis of its effects on individual ceramide (Cer) and sphingomyelin (SM) species. As expected, the total Cer content decreased by half in the lungs of FB1-exposed piglets, while in contrast, total Cer increased 3.5-fold in the livers of FB1-exposed animals. Our data also indicated that FB1 is more prone to bind to CerS4 and CerS2 to deplete lung and to enrich liver in d18:1/C20:0 and d18:1/C22:0 ceramides and to interact with CerS1 to enrich liver in d18:1/C18:0 ceramides. Cer levels were counterbalanced by those of SM. In conclusion, these results demonstrated that the specificity of the effects of FB1 on tissues and organs is due to the effects of the toxin on CerS4, CerS2 and CerS1.
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hal-03331305 , version 1 (01-09-2021)

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Paternité - Pas d'utilisation commerciale - Pas de modification

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Citer

Nicolas Loiseau, Arnaud Polizzi, Aude Dupuy, Nicole Therville, Mirindra Rakotonirainy, et al.. New insights into the organ-specific adverse effects of fumonisin B1: comparison between lung and liver. Archives of Toxicology, 2015, 89 (9), pp.1619-1629. ⟨10.1007/s00204-014-1323-6⟩. ⟨hal-03331305⟩
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