The effect of fumonisin B1 on developing chick embryos: correlation between de novo sphingolipid biosynthesis and gross morphological changes |
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Authors: | Claudia Zacharias Gerhild Van Echten-Deckert Elaine Wang Alfred H. Merrill Jr. Konrad Sandhoff |
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Affiliation: | (1) Institut für Organische Chemie und Biochemie der Universität Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany;(2) Department of Biochemistry, Rollins Research Center, Emory University School of Medicine, 30322 Atlanta, Georgia, USA |
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Abstract: | Fumonisins, mycotoxins produced byFusarium moniliforme and a number of other fungi, are potent inhibitors of the sphinganine-N-acyltransferase, a key enzyme of sphingolipid biosynthesis, and cause neuronal degeneration, liver and renal toxicity, cancer and other injury to animals.In this study we investigated the effect of fumonisin B1 on the sphingolipids of developing chick embryos. After yolk sac injection of fumonisin B1 a concentration and time dependent increase of the sphinganine-over-sphingosine ratio of the embryos could be demonstrated. Studies were done to evaluate the effect of fumonisin B1 on the glycosphingolipid pattern of the chick embryos. In the presence of 72 µg fumonisin B1 per egg the incorporation of [14C]galactose and of [14C]serine into embryonic glycosphingolipids was reduced by about 70%, although the mass of glycosphingolipids was not affected by the toxin. However, a reduction of the wet weight of the treated embryos was observed. Additionally, histological examinations of whole embryo sections of control and fumonisin B1 treated embryos are presented. Fumonisin B1 caused haemorrhages under the skin as well as in the liver of treated embyros. A close correlation between disruption of sphingoid metabolism and light microscopic detectable tissue lesions could be observed.Abbreviations Cer ceramide (N-acylsphingosine) - FB1 fumonisin B1 - GM3 NeuAc23Gal14Glc11Cer - GD3 NeuAc28NeuAc23Gal14Glc11Cer - GD1a NeuAc23Gal13GalNAc14(NeuAc23)Gal14Glc11Cer - GT1b NeuAc23Gal13GalNAc14(NeuAc28NeuAc23) Gal14Glc11Cer - HPLC high pressure liquid chromatography - PBS phosphate buffered saline - PDMP 1-phenyl-2-dodecanoylamino-3-morpholino-1-propanol - Sa sphinganine - So sphingosine - Sa/So sphinganine-over-sphingosine - TLC thin layer chromatography - Tris Tris(hydroxymethyl)aminomethanDedicated to Dr Sen-itiroh Hakomori in celebration of his 65th birthday. |
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Keywords: | chick embryo fumonisin B1 glycosphingolipid biosynthesis sphingoid bases |
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