Effect of fumonisin B1 on phosphatidylethanolamine biosynthesis in Chinese hamster ovary cells.
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.
Badiani
K
K
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
Byers
D M
DM
Cook
H W
HW
Ridgway
N D
ND
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
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