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Identification of N ‐acyl‐fumonisin B 1 as new cytotoxic metabolites of fumonisin mycotoxins
Author(s) -
Harrer Henning,
Laviad Elad L.,
Humpf Hans Ulrich,
Futerman Anthony H.
Publication year - 2013
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.201200465
Subject(s) - fumonisin b1 , ceramide synthase , fumonisin , biochemistry , mycotoxin , acylation , chemistry , cytotoxicity , ceramide , biology , in vitro , apoptosis , food science , catalysis
Scope Fumonisins are mycotoxins produced by F usarium species. The predominant derivative, fumonisin B 1 ( FB 1), occurs in food and feed and is of health concern due to its hepatotoxic and carcinogenic effects. However, the role of FB 1 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 ( C er S ) genes. N ‐acyl‐ FB 1 derivatives were detected as new metabolites in cultured cells at levels of up to 10 pmol/mg of protein. The N ‐ acylation of FB 1 and hydrolyzed FB 1 was analyzed in several cell lines, including cells overexpressing C er S . The acyl‐chain length of the N ‐acyl fumonisins depends on the C er S isoform acylating them. The N ‐acyl fumonisins are more cytotoxic than the parent fumonisin B 1. Conclusion 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.