title: [Induction of apoptosis in cultured human proximal tubule cells by fumonisins and fumonisin metabolites].
abstract: 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.
authors.affiliation: Lehrstuhl für Lebensmittelchemie, Universität Würzburg, Am Hubland, 97074, Würzburg.
authors.forename: W
authors.initials: W
authors.lastname: Seefelder
authors.forename: H U
authors.initials: HU
authors.lastname: Humpf
authors.forename: G
authors.initials: G
authors.lastname: Schwerdt
authors.forename: R
authors.initials: R
authors.lastname: Freudinger
authors.forename: M
authors.initials: M
authors.lastname: Gekle