Liscovitch M, Blusztajn J K, Freese A, Wurtman R J
Biochem J. 1987 Jan 1;241(1):81-6. doi: 10.1042/bj2410081.
The effects of the potent tumour-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) on phosphatidylcholine (PtdCho) metabolism were investigated in the neuroblastoma X glioma hybrid cell line NG108-15. TPA (100 nM) stimulated by 150-200% the release into the medium of 3H radioactivity from cells that had been pre-labelled with [3H]choline. H.p.l.c. analysis of the medium revealed that TPA stimulated the release of only free [3H]choline (212 +/- 11% of control), without affecting such other labelled metabolites as [3H]phosphocholine and [3H]glycerophosphocholine. This effect was concentration-dependent, with a half-maximal effect obtained at 27.5 +/- 6.8 nM, and was observable as early as 5-10 min after exposure to TPA. The TPA-induced release of [3H]choline into the medium was accompanied by a small and variable decrease in cellular [3H]PtdCho (to 93 +/- 4% of control). However, the radioactivity associated with water-soluble cellular choline metabolites (mainly [3H]phosphocholine and [3H]glycerophosphocholine) remained unchanged. TPA also stimulated the release of [3H]choline derived from [3H]PtdCho that had been produced via the methylation pathway from [3H]methionine. These data suggest that phosphatidylcholine may serve as the source of free choline released from the cells in response to TPA. The possible enzymic mechanisms underlying this response are discussed.
在神经母细胞瘤X胶质瘤杂交细胞系NG108 - 15中研究了强效肿瘤促进剂佛波醇酯12 - O - 十四烷酰佛波醇13 - 乙酸酯（TPA）对磷脂酰胆碱（PtdCho）代谢的影响。TPA（100 nM）使预先用[3H]胆碱标记的细胞释放到培养基中的3H放射性增加了150 - 200%。对培养基的高效液相色谱分析表明，TPA仅刺激游离[3H]胆碱的释放（为对照的212±11%），而不影响其他标记代谢物，如[3H]磷酸胆碱和[3H]甘油磷酸胆碱。这种效应具有浓度依赖性，在27.5±6.8 nM时达到半数最大效应，并且在接触TPA后5 - 10分钟即可观察到。TPA诱导的[3H]胆碱释放到培养基中伴随着细胞内[3H]PtdCho的小幅且可变的减少（降至对照的93±4%）。然而，与水溶性细胞胆碱代谢物（主要是[3H]磷酸胆碱和[3H]甘油磷酸胆碱）相关的放射性保持不变。TPA还刺激了源自通过[3H]甲硫氨酸甲基化途径产生的[3H]PtdCho的[3H]胆碱的释放。这些数据表明，磷脂酰胆碱可能是细胞响应TPA释放的游离胆碱的来源。讨论了这种反应潜在的酶促机制。
