title: Effect of fumonisin B1 on phosphatidylethanolamine biosynthesis in Chinese hamster ovary cells.
abstract: Fumonisin B1 has been shown to inhibit dihydroceramide synthesis and elevate cellular sphinganine levels in several cultured cell lines. In Chinese hamster ovary (CHO)-K1 cells, 20 microM fumonisin B1 inhibited sphingomyelin synthesis by 75% after 5 h, but stimulated [3H]serine incorporation into PtdEtn by 5- to 7-fold. Fumonisin caused a 10-20% increase in [3H]serine labelling of PtdSer. While fumonisin (20 microM) caused sustained inhibition of sphingomyelin synthesis, PtdEtn labelling peaked at 7-fold above controls at 12 h and declined to 4-fold by 24 h. Fumonisin treatment for 12 h increased the in vitro activity of PtdSer synthase by 62% and inhibited PtdSer decarboxylase by 35%, suggesting that increased PtdEtn labelling by [3H]serine is not by this pathway. An ethanolamine 'trap' experiment was performed to assess the contribution of phosphoethanolamine from sphinganine degradation for PtdEtn labelling. Stimulation of [3H]serine incorporation into PtdEtn by fumonisin could be reduced by 60% with the inclusion of 50 microM unlabelled ethanolamine in the culture medium. The ethanolamine-mediated reduction in [3H]serine incorporation into PtdEtn was accompanied by 4-fold increase in cellular [3H]phosphoethanolamine. In control cells labelled with [3H]serine, 50 microM ethanolamine did not cause [3H]phosphoethanolamine to accumulate. Consistent with elevated phosphoethanolamine production in fumonisin-treated cells, [3H]ethanolamine incorporation into PtdEtn was inhibited by 75% after 12 h. The degradation of endogenous long-chain bases to phosphoethanolamine and entry into the CDP-ethanolamine pathway appears to be a major pathway for PtdEtn synthesis in fumonisin-treated CHO-K1 cells.
authors.affiliation: Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Badiani
authors.forename: D M
authors.initials: DM
authors.lastname: Byers
authors.forename: H W
authors.initials: HW
authors.lastname: Cook
authors.forename: N D
authors.initials: ND
authors.lastname: Ridgway
mesh_terms: D000818:Animals; D016466:CHO Cells; D002262:Carboxy-Lyases / Q000378:metabolism; D006224:Cricetinae; D019856:Ethanolamine; D004983:Ethanolamines / Q000494:pharmacology; D037341:Fumonisins; D009183:Mycotoxins / Q000494:pharmacology*; D019884:Nitrogenous Group Transferases; D010714:Phosphatidylethanolamines / Q000096:biosynthesis* / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D014166:Transferases / Q000378:metabolism
chemical_list: D004983:Ethanolamines; D037341:Fumonisins; D009183:Mycotoxins; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D013109:Sphingomyelins; C056933:fumonisin B1; D012694:Serine; D019856:Ethanolamine; D014166:Transferases; D019884:Nitrogenous Group Transferases; C022370:phospholipid serine base exchange enzyme; D002262:Carboxy-Lyases; C022353:phosphatidylserine decarboxylase; D013110:Sphingosine; C005682:safingol