Fumonisin B1 induces apoptosis in cultured human keratinocytes through sphinganine accumulation and ceramide depletion.

Tolleson,W H; Couch,L H; Melchior,W B; Jenkins,G R; Muskhelishvili,M; Muskhelishvili,L; McGarrity,L J; Domon,O; Morris,S M; Howard,P C

doi:10.3892/ijo.14.5.833

Fumonisin B1 induces apoptosis in cultured human keratinocytes through sphinganine accumulation and ceramide depletion.

Authors:
- W H Tolleson
- L H Couch
- W B Melchior
- G R Jenkins
- M Muskhelishvili
- L Muskhelishvili
- L J McGarrity
- O Domon
- S M Morris
- P C Howard
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Affiliations: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, USA.
Published online on: May 1, 1999 https://doi.org/10.3892/ijo.14.5.833
Pages: 833-876

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Abstract

Fumonisin B1 stimulates apoptosis in a variety of cell types and tissues. We examined the role of sphingolipid changes in fumonisin B1-stimulated apoptosis. Sphinganine accumulated rapidly, sphingosine levels remained unchanged, and ceramides decreased during fumonisin B1 exposure. Increased DNA fragmentation, decreased viability, and apoptotic morphology were observed in cells exposed to fumonisin B1, sphinganine, or N-acetylsphingosine. Co-exposure to N-acetylsphingosine or beta-chloroalanine, which blocks sphinganine accumulation, partially protected cells from fumonisin B1-induced apoptosis. These results illustrate three sphingolipid-dependent mechanisms for inducing apoptosis: accumulation of excess ceramide, accumulation of excess sphinganine, and depletion of ceramide or complex sphingolipids derived from ceramide.