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乙醇抑制人白血病单核细胞样U937细胞中磷脂酰胆碱和磷脂酰乙醇胺的生物合成。

Ethanol inhibits phosphatidylcholine and phosphatidylethanolamine biosynthesis in human leukemic monocyte-like U937 cells.

作者信息

Chu A J, Nguyen C T

机构信息

Miami Heart Institute, Miami Beach, FL 33140-2999.

出版信息

Cell Biochem Funct. 1993 Jun;11(2):107-17. doi: 10.1002/cbf.290110206.

DOI:10.1002/cbf.290110206
PMID:8324879
Abstract

The effect of ethanol (ETOH) on the incorporation of [14C]oleic acid (18:1) into lipid in human monocyte-like U937 cells was investigated. With increasing time of exposure to ETOH, the percentage of the label distributed into neutral lipid (NL) declined from 35 per cent (3 h) to 10 per cent (24 h) accompanied by increased incorporation into phospholipid (PL). [14C] 18:1 was preferentially incorporated into triglyceride (TG) and phosphatidylcholine (PC), comprising over 65 per cent and 50 per cent of the label associated with NL and PL, respectively. Low concentrations of ETOH (< or = 1.0 per cent; v/v) had no effect. At concentrations greater than 1.5 per cent, there was enhanced incorporation into TG and diacylglycerol (DAG) in a 24-h incubation period, while at 16 h the label in phosphatidylethanolamine (PE) was decreased. The effect of ETOH on the CDP-choline or ethanolamine pathway was examined by monitoring the incorporation of [3H]choline or [14C]ethanolamine into PC or PE, respectively. At low concentrations ETOH had no effect on either choline uptake or the incorporation into PC. Higher concentrations (> or = 1.5 per cent) for 3 and 6 h resulted in a slightly decreased choline uptake, and the reduction (40-50 per cent) of incorporation into PC suggests that the CDP-choline pathway was inhibited. There was a similar inhibition of the incorporation of [14C]ethanolamine into PE. When the cells were incubated for 3 h in the presence of 2 per cent ETOH and with labelled 18:1 and PL-base, the ratios of incorporation (base/18:1) into PC and PE fractions decreased, indicating that the major inhibition lay in blockage of the availability of the base moiety for PL formation. Analysis of the distribution of the label into metabolites revealed that ETOH inhibited the conversion of [14C]ethanolamine into [14C]phosphorylethanolamine. The reduction in incorporation was not due to the enhanced breakdown of base-labelled PL. Our results indicate that ETOH has an inhibitory effect on the CDP-choline or ethanolamine pathway.

摘要

研究了乙醇(ETOH)对人单核细胞样U937细胞中[14C]油酸(18:1)掺入脂质的影响。随着暴露于ETOH时间的增加,分布到中性脂质(NL)中的标记物百分比从35%(3小时)降至10%(24小时),同时掺入磷脂(PL)中的量增加。[14C]18:1优先掺入甘油三酯(TG)和磷脂酰胆碱(PC),分别占与NL和PL相关标记物的65%以上和50%以上。低浓度的ETOH(≤1.0%;v/v)没有影响。在浓度大于1.5%时,在24小时的孵育期内掺入TG和二酰基甘油(DAG)的量增加,而在16小时时磷脂酰乙醇胺(PE)中的标记物减少。通过分别监测[3H]胆碱或[14C]乙醇胺掺入PC或PE来研究ETOH对CDP - 胆碱或乙醇胺途径的影响。在低浓度下,ETOH对胆碱摄取或掺入PC均无影响。较高浓度(≥1.5%)处理3小时和6小时导致胆碱摄取略有下降,并且掺入PC的量减少(40 - 50%)表明CDP - 胆碱途径受到抑制。[14C]乙醇胺掺入PE也有类似的抑制作用。当细胞在2% ETOH存在下与标记的18:1和PL - 碱基孵育3小时时,掺入PC和PE组分的比例(碱基/18:1)降低,表明主要抑制在于阻止碱基部分用于PL形成。对标记物在代谢产物中的分布分析表明,ETOH抑制[14C]乙醇胺转化为[14C]磷酸乙醇胺。掺入量的减少不是由于碱基标记的PL分解增强。我们的结果表明,ETOH对CDP - 胆碱或乙醇胺途径具有抑制作用。

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