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Abstract

FB1 is a fungal toxin produced by Fusarium verticillioides that inhibits ceramide synthase, a key enzyme in the de novo sphingolipid biosynthesis pathway. The purpose of this study was to determine changes in expression of p42 MAP kinase (pERK2) in response to FB1 in LLC-PK1 cells. Significant inhibition of cell growth was first noted after 48 h exposure to FB1, but pERK2 expression was decreased at 24 h. Serine palmitoyltransferase (SPT) inhibitors and the glucosylceramide synthase inhibitor, PDMP, did not reverse the decreased expression of pERK2 caused by FB1. However, each SPT inhibitor alone or PDMP also caused a decreased expression of pERK2, indicating that FB1-mediated changes in expression of pERK2 could be independent of alterations in sphingoid bases but dependent on de novo sphingolipid biosynthesis.

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