Gillies R J, Barry J A, Ross B D
Department of Biochemistry, University of Arizona HSC, Tucson 85724.
Magn Reson Med. 1994 Sep;32(3):310-8. doi: 10.1002/mrm.1910320306.
In vivo magnetic resonance spectroscopy (MRS) has revealed that phosphomonoesters (PME) such as phosphocholine (PCho) and phosphoethanolamine (PEth) are elevated in tumors and rapidly proliferating tissues. The regulation of PME levels and their relationship to proliferation are not well known. In the present study, we investigated the regulation of PCho and PEth levels in rat glioma cells grown in vivo and in vitro using 31P and 13C MRS. However, the ability of cells to produce choline endogenously is variable. To fully understand regulation of PCho levels, it is necessary to characterize the activity of the endogenous pathway, if it exists. This was first investigated by following the metabolic fate of 13C-labeled methionine of 9L glioma tumors in vivo. Our results indicate that there is a significant amount of de novo choline synthesis in vivo. However, similar experiments performed in vitro using cells cultured in bioreactors indicated that glioma cells themselves are unable to synthesize choline de novo, suggesting that the in vivo results were due to the involvement of extra-tumoral organs, e.g., liver. Further in vitro experiments demonstrated that the uptake and phosphorylation of physiologically relevant concentrations of exogenous choline is very active in these systems. Thus, it appears that the exogenous pathway for PCho biosynthesis predominates and regulates PCho levels in glioma cells. Our results also demonstrate that PCho levels are lowest, and PEth levels are highest, in non-proliferating cells. These observations indicate that there is a decrease in the biosynthesis of PCho concomitant with a reduction in culture growth. The source of the increased PEth is, as yet, undefined.
体内磁共振波谱（MRS）显示，磷酸单酯（PME）如磷酸胆碱（PCho）和磷酸乙醇胺（PEth）在肿瘤和快速增殖组织中升高。PME水平的调节及其与增殖的关系尚不清楚。在本研究中，我们使用31P和13C MRS研究了体内和体外培养的大鼠胶质瘤细胞中PCho和PEth水平的调节。然而，细胞内源性产生胆碱的能力是可变的。为了充分了解PCho水平的调节，有必要表征内源性途径（如果存在）的活性。这首先通过追踪体内9L胶质瘤肿瘤中13C标记蛋氨酸的代谢命运来进行研究。我们的结果表明，体内存在大量的从头合成胆碱的过程。然而，在生物反应器中培养细胞进行的体外类似实验表明，胶质瘤细胞本身无法从头合成胆碱，这表明体内结果是由于肿瘤外器官（如肝脏）的参与。进一步的体外实验表明，在这些系统中，生理相关浓度的外源性胆碱的摄取和磷酸化非常活跃。因此，似乎PCho生物合成的外源性途径占主导地位并调节胶质瘤细胞中的PCho水平。我们的结果还表明，在非增殖细胞中，PCho水平最低，PEth水平最高。这些观察结果表明，随着培养生长的减少，PCho的生物合成也减少。PEth增加的来源尚未确定。
