These authors contributed equally to this work.
Identification of N-acyl-fumonisin B1 as new cytotoxic metabolites of fumonisin mycotoxins
Article first published online: 23 DEC 2012
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 57, Issue 3, pages 516–522, March 2013
How to Cite
Harrer, H., Laviad, E. L., Humpf, H. U. and Futerman, A. H. (2013), Identification of N-acyl-fumonisin B1 as new cytotoxic metabolites of fumonisin mycotoxins. Mol. Nutr. Food Res., 57: 516–522. doi: 10.1002/mnfr.201200465
- Issue published online: 12 MAR 2013
- Article first published online: 23 DEC 2012
- Manuscript Accepted: 5 NOV 2012
- Manuscript Revised: 20 OCT 2012
- Manuscript Received: 19 JUL 2012
- German-Israeli Foundation for scientific research and development. Grant Number: GIF 844/2004
- German Research Foundation. Grant Number: DFG HU 730/1-8
Fumonisins are mycotoxins produced by Fusarium species. The predominant derivative, fumonisin B1 (FB1), occurs in food and feed and is of health concern due to its hepatotoxic and carcinogenic effects. However, the role of FB1 metabolites on the mechanism of the toxicity, the inhibition of the ceramide synthesis, is unknown. The aim of this study was to identify new fumonisin metabolites and to evaluate their cytotoxic potential.
Methods and results
MS, molecular biology, and in vitro enzyme assays were used to investigate fumonisin metabolism in mammalian cells overexpressing human ceramide synthase (CerS) genes. N-acyl-FB1 derivatives were detected as new metabolites in cultured cells at levels of up to 10 pmol/mg of protein. The N-acylation of FB1 and hydrolyzed FB1 was analyzed in several cell lines, including cells overexpressing CerS. The acyl-chain length of the N-acyl fumonisins depends on the CerS isoform acylating them. The N-acyl fumonisins are more cytotoxic than the parent fumonisin B1.
The identification of N-acyl fumonisins with various acyl chain lengths together with the observed cytotoxicity of these compounds is a new aspect of fumonisin-related toxicity. Therefore, these new metabolites might play an important role in the mode of action of fumonisins.