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Induction of apoptosis in cultured human proximal tubule cells by fumonisins and fumonisin metabolites

Abstract

Fumonisin B{sub 1} (FB{sub 1}) causes apoptosis in a variety of cell types and tissues but the apoptotic potential of other fumonisins and fumonisin metabolites has not been determined and the underlying mechanisms are not completely understood. In our studies we exposed human proximal tubule-derived cells (IHKE cells) to FB{sub 1}, fumonisin B{sub 2} (FB{sub 2}), fumonisin B{sub 3} (FB{sub 3}), hydrolyzed fumonisin B{sub 1} (HFB{sub 1}) and N-palmitoyl-hydrolyzed fumonisin B{sub 1} (N-Pal-HFB{sub 1}) and investigated caspase-3 activation, chromatin condensation and DNA fragmentation. Exposure to 10 {mu}mol/L FB{sub 1} for 24 h led to a significant increase in caspase-3 activity, chromatin condensation and to DNA fragmentation. All other tested compounds did not show any significant activation of caspase-3 activity nor chromatin condensation and DNA-fragmentation. Furthermore, we examined if a sphinganine accumulation is correlated with an induction of apoptosis in IHKE cells. Therefore we used a liquid chromatography/electrospray ionization-mass spectrometry(LC/ESI-MS)-method using phytosphingosine as an internal standard to determine sphinganine and sphingosine concentrations in IHKE cells. Whereas a significant increase of sphinganine (up to 7000% compared to control cells) was observed with all fumonisin-derivates, sphingosine levels nearly remained unchanged indicating that all substrates inhibited ceramide synthase effectively. These results demonstrate that all  More>>
Publication Date:
Oct 15, 2003
Product Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 192; Journal Issue: 2; Other Information: DOI: 10.1016/S0041-008X(03)00262-X; PII: S0041008X0300262X; Copyright (c) 2003 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); PBD: 15 Oct 2003
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BIOLOGICAL EFFECTS; ENZYME INHIBITORS; LIGASES; METABOLITES; TOXIC MATERIALS; TOXICITY
OSTI ID:
20468306
Country of Origin:
United States
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 0041-008X; TXAPA9; TRN: US04R1737044004
Submitting Site:
INIS
Size:
page(s) 146-153
Announcement Date:

Citation Formats

Seefelder, W, Humpf, H -U, Schwerdt, G, Freudinger, R, and Gekle, M. Induction of apoptosis in cultured human proximal tubule cells by fumonisins and fumonisin metabolites. United States: N. p., 2003. Web. doi:10.1016/S0041-008X(03)00262-X.
Seefelder, W, Humpf, H -U, Schwerdt, G, Freudinger, R, & Gekle, M. Induction of apoptosis in cultured human proximal tubule cells by fumonisins and fumonisin metabolites. United States. doi:10.1016/S0041-008X(03)00262-X.
Seefelder, W, Humpf, H -U, Schwerdt, G, Freudinger, R, and Gekle, M. 2003. "Induction of apoptosis in cultured human proximal tubule cells by fumonisins and fumonisin metabolites." United States. doi:10.1016/S0041-008X(03)00262-X. https://www.osti.gov/servlets/purl/10.1016/S0041-008X(03)00262-X.
@misc{etde_20468306,
title = {Induction of apoptosis in cultured human proximal tubule cells by fumonisins and fumonisin metabolites}
author = {Seefelder, W, Humpf, H -U, Schwerdt, G, Freudinger, R, and Gekle, M}
abstractNote = {Fumonisin B{sub 1} (FB{sub 1}) causes apoptosis in a variety of cell types and tissues but the apoptotic potential of other fumonisins and fumonisin metabolites has not been determined and the underlying mechanisms are not completely understood. In our studies we exposed human proximal tubule-derived cells (IHKE cells) to FB{sub 1}, fumonisin B{sub 2} (FB{sub 2}), fumonisin B{sub 3} (FB{sub 3}), hydrolyzed fumonisin B{sub 1} (HFB{sub 1}) and N-palmitoyl-hydrolyzed fumonisin B{sub 1} (N-Pal-HFB{sub 1}) and investigated caspase-3 activation, chromatin condensation and DNA fragmentation. Exposure to 10 {mu}mol/L FB{sub 1} for 24 h led to a significant increase in caspase-3 activity, chromatin condensation and to DNA fragmentation. All other tested compounds did not show any significant activation of caspase-3 activity nor chromatin condensation and DNA-fragmentation. Furthermore, we examined if a sphinganine accumulation is correlated with an induction of apoptosis in IHKE cells. Therefore we used a liquid chromatography/electrospray ionization-mass spectrometry(LC/ESI-MS)-method using phytosphingosine as an internal standard to determine sphinganine and sphingosine concentrations in IHKE cells. Whereas a significant increase of sphinganine (up to 7000% compared to control cells) was observed with all fumonisin-derivates, sphingosine levels nearly remained unchanged indicating that all substrates inhibited ceramide synthase effectively. These results demonstrate that all compounds let to increased sphinganine levels in IHKE cells but only FB{sub 1} was able to induce apoptosis. We conclude that the inhibition of the ceramide synthase is not per se a predictor whether or not fumonisins induce apoptosis.}
doi = {10.1016/S0041-008X(03)00262-X}
journal = {Toxicology and Applied Pharmacology}
issue = {2}
volume = {192}
journal type = {AC}
place = {United States}
year = {2003}
month = {Oct}
}