
It is well-known that fumonisin B1 (FB1) stimulates apoptosis in a variety of cell types and tissues but the apoptotic potential of other fumonisins and fumonisin metabolites has not been investigated. In our studies we exposed human proximal tubule-derived cells (IHKE cells) to FB1, fumonisin B2 (FB2), hydrolyzed fumonisin B1 (HFB1) and N-palmitoyl-hydrolyzed fumonisin B1 (N-Pal-HFB1) and investigated caspase 3 activation and DNA fragmentation. Only exposure to 10 μmol/L FB1 for 24h led to a significantly increased activity of caspase 3 and to DNA fragmentation. All other compounds tested did not show any significant activation of caspase 3 activity. Further we examined wether a sphinganine accumulation is correlated with the induction of apoptosis in IHKE cells. Therefore we developed a liquid chromato-graphy/electrospray ionization-tandem-mass spectrometry(HPLC-MS/MS)-method using phytosphingosine as an internal standard to determine sphinganine- and sphingosine concentrations in incubated IHKE cells. Whereas a significant increase of sphinganine was observed with all substrates, sphingosine levels remained unchanged. This shows that FB1 exposure leads to apoptosis in a sphinganine-independent mechanism.
Kidney Tubules, Proximal, Spectrometry, Mass, Electrospray Ionization, Caspase 3, Sphingosine, Caspases, Humans, Apoptosis, Fumonisins, Cells, Cultured, Chromatin, Chromatography, Liquid
Kidney Tubules, Proximal, Spectrometry, Mass, Electrospray Ionization, Caspase 3, Sphingosine, Caspases, Humans, Apoptosis, Fumonisins, Cells, Cultured, Chromatin, Chromatography, Liquid
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