Influence of platelet-activating factor, lyso-platelet-activating factor and edelfosine on Langmuir monolayers imitating plasma membranes of cell lines differing in susceptibility to anti-cancer treatment: the effect of plasmalogen level

Influence of platelet-activating factor, lyso-platelet-activating factor and edelfosine on Langmuir monolayers imitating plasma membranes of cell lines differing in susceptibility to anti-cancer treatment: the effect of plasmalogen level
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DOI:
10.1098/rsif.2013.1103
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发表时间:
2014-06-06
影响因子:
3.9
通讯作者:
Dynarowicz-Latka, Patrycja
Dynarowicz-Latka, Patrycja
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Flasinski, Michal;Hac-Wydro, Katarzyna;Dynarowicz-Latka, Patrycja

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在模仿天然膜的朗缪尔单层膜中研究了三种结构相关但生物活性不同的单链醚磷脂(PAF(血小板激活因子)和溶血-PAF)和抗癌药物(edelfosine (ED))。进行实验的目的是研究这些脂质对模拟 ED 抗癌活性易感性不同的细胞系(即早幼粒细胞白血病细胞 (HL-60) 和早幼粒细胞白血病细胞 (K-562))质膜的单层影响。由于这些细胞在胆固醇/磷脂比率和膜中缩醛磷脂浓度方面存在本质差异,因此我们在各种成分的人工系统中进行了系统研究。将模型白血病细胞膜的结果与模拟正常白细胞的系统获得的数据进行比较。我们的结果表明,缩醛磷脂的水平显着调节单链磷脂对所研究系统的影响。实验还证实,与K-562相比,醚脂与HL-60细胞模型膜(在对ED敏感的生物测试中)的相互作用具有相反的特征,对ED有抵抗力。此外,表征作为膜模型的单层的参数值(相互作用的强度、单层的流动性和形态)证明了这些细胞对 ED 的敏感性以及对 PAF 的敏感性。有趣的是,我们发现,通常被描述为 PAF 无活性前体的 lyso-PAF 对 HL-60 模型膜的影响比 ED 更强。
Three structurally related but differing in biological activities single-chained ether phospholipids (PAF (platelet-activating factor) and lyso-PAF) and an anti-cancer drug (edelfosine (ED)) were investigated in Langmuir monolayers imitating natural membranes. The aim of the undertaken experiments was to study the influence of these lipids on monolayers mimicking plasma membranes of cell lines differing in susceptibility to the anti-cancer activity of ED, i.e. promyelocytic leukaemia cells (HL-60) and promyeloblastic leukaemia cells (K-562). As these cells differ essentially in the cholesterol/phospholipid ratio and plasmalogen concentration in the membrane, we have carried out systematic investigations in artificial systems of various compositions. The results for model leukaemia cell membrane were compared with data acquired for systems imitating normal leucocytes. Our results show that the level of plasmalogens significantly modulates the influence of the single-chained phospholipids on the investigated systems. The experiments confirmed also that the interactions of ether lipidswith amodelmembrane of HL-60 cells (in biological tests sensitive to ED) have opposite character when compared with K-562, being resistant to ED. Moreover, the values of the parameters characterizing monolayers serving as membrane models (strength of interactions, monolayers fluidity and morphology) proved both sensitivity of these cells to ED and lack of their susceptibility towards PAF. Interestingly, it has been found that lyso-PAF, which is usually described as an inactive precursor of PAF, displays a stronger effect on HL-60 model membranes than ED.