Liscovitch M, Freese A, Blusztajn J K, Wurtman R J
J Neurochem. 1986 Dec;47(6):1936-41. doi: 10.1111/j.1471-4159.1986.tb13111.x.
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.
我们研究了佛波酯对神经母细胞瘤 - 胶质瘤杂交细胞系NG108 - 15中磷脂酰胆碱（PtdCho）代谢的影响。100 nM的12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）在37℃孵育2小时期间，刺激[3H]胆碱掺入PtdCho的量增加了两倍。TPA的这种作用具有浓度依赖性，其EC50为24.5±4.4 nM。TPA的作用也具有时间依赖性，并且仅在15 - 30分钟的延迟期后才变得明显。TPA还以与PtdCho含量变化平行的浓度和时间依赖性方式降低了[3H]胆碱掺入水溶性细胞成分中的量。对该池的HPLC分析表明，其主要成分（85 - 95%）[3H]磷酸胆碱的水平降低了29±5%，而[3H]甘油磷酸胆碱（该池的0.5 - 2%）的水平增加了84±4%。当用[3H]胆碱脉冲标记细胞并在TPA存在下进行追踪时，PtdCho标记也受到刺激。TPA不影响[3H]肌醇、[14C]乙醇胺或[14C]丝氨酸掺入磷脂。非促肿瘤化合物佛波醇和4α - 佛波醇 - 12,13 - 二癸酸酯（100 nM）在调节胆碱掺入方面完全无效，而生物活性类似物4β - 佛波醇 - 12,13 - 二癸酸酯和4β - 佛波醇 - 12,13 - 二丁酸酯与TPA一样有效。我们得出结论，促肿瘤佛波酯可以调节神经源性细胞中的PtdCho代谢。讨论了介导这种作用的机制以及PtdCho代谢在正常信号转导事件和肿瘤促进剂的生物学作用中可能的参与情况。
