Phosphatidylcholine biosynthesis in the neuroblastoma-glioma hybrid cell line NG108-15: stimulation by phorbol esters.
We have examined the effects of phorbol esters on phosphatidylcholine (PtdCho) metabolism in the neuroblastoma-glioma hybrid cell line NG108-15. 12-O-Tetradecanoylphorbol-13-acetate (TPA), 100 nM, stimulated twofold the incorporation of [3H]choline into PtdCho during 2 h of incubation at 37 degrees C. This effect of TPA was concentration dependent, exhibiting an EC50 of 24.5 +/- 4.4 nM. The effect of TPA was also time dependent and became apparent only after a lag period of 15-30 min. TPA also decreased the incorporation of [3H]choline into water-soluble cellular constituents in a manner whose concentration and time-dependence paralleled the changes observed in PtdCho content. HPLC analysis of this pool revealed that the levels of its major (85-95%) constituent, [3H]phosphocholine, were decreased by 29 +/- 5%, whereas those of [3H]glycerophosphocholine (0.5-2% of the pool) were increased by 84 +/- 4%. PtdCho labeling was also stimulated when cells were pulse labeled with [3H]choline and chased in the presence of TPA. The incorporation of [3H]inositol, [14C]ethanolamine, or [14C]serine into phospholipids was not affected by TPA. The non-tumor-promoting compounds phorbol and 4 alpha-phorbol-12,13-didecanoate (at 100 nM) were completely ineffective in modulating choline incorporation, whereas the biologically active analogs 4 beta-phorbol-12,13-didecanoate and 4 beta-phorbol-12,13-dibutyrate were as effective as TPA. We conclude that tumor-promoting phorbol esters can modulate PtdCho metabolism in neural-derived cells. The mechanisms mediating this effect and the possible involvement of PtdCho metabolism in normal signal transduction events and in the biological actions of tumor promoters are discussed.
D000818:Animals; D002460:Cell Line; D002794:Choline / Q000378:metabolism; D019856:Ethanolamine; D004983:Ethanolamines / Q000378:metabolism; D005910:Glioma / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004983:Ethanolamines; D010703:Phorbol Esters; D010713:Phosphatidylcholines; D007294:Inositol; D019856:Ethanolamine; D002794:Choline; D013755:Tetradecanoylphorbol Acetate