Heczková Bohdana, Slotte J Peter
Department of Biochemistry and Pharmacy, Abo Akademi University, Tykistokatu 6A, 20520 Turku, Finland.
FEBS Lett. 2006 May 1;580(10):2471-6. doi: 10.1016/j.febslet.2006.03.079. Epub 2006 Apr 7.
1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (OMPC, edelfosine) and 1-hexadecylphosphocholine (HePC, miltefosine) represent two groups of synthetic ether lipid analogues with anti-tumor activity. Because of their hydrophobic nature, they may become incorporated into plasma membranes of cells, and it has been argued that they may act via association with lipid rafts. With the quenching of steady-state fluorescence of probes preferentially partitioning into sterol-rich ordered domains (cholestatrienol and trans-parinaric acid), we showed that OMPC and HePC by themselves did not form sterol-rich domains in fluid model membranes, in contrast to the two chain ether lipid 1,2-O-dihexadecyl-sn-glycero-3-phosphocholine. Nevertheless, all three ether lipids significantly stabilized palmitoyl-sphingomyelin/cholesterol-rich domains against temperature induced melting. In conclusion, this study shows that anti-tumor ether lipids are likely to affect the properties of cholesterol-sphingomyelin domains (i.e., lipid rafts) when incorporated into cell membranes.
1 - O - 十八烷基 - 2 - O - 甲基 - sn - 甘油 - 3 - 磷酸胆碱（OMPC，依德膦）和1 - 十六烷基磷胆碱（HePC，米替福新）代表两组具有抗肿瘤活性的合成醚脂类似物。由于它们的疏水性，它们可能会掺入细胞膜中，并且有人认为它们可能通过与脂筏结合而起作用。通过优先分配到富含甾醇的有序结构域（胆甾三烯醇和反式 - 紫黄质酸）中的探针的稳态荧光猝灭，我们表明，与双链醚脂1,2 - O - 二己基 - sn - 甘油 - 3 - 磷酸胆碱相反，OMPC和HePC自身在流体模型膜中不会形成富含甾醇的结构域。然而，所有三种醚脂都能显著稳定棕榈酰鞘磷脂/富含胆固醇的结构域，防止温度诱导的熔化。总之，这项研究表明，抗肿瘤醚脂掺入细胞膜时可能会影响胆固醇 - 鞘磷脂结构域（即脂筏）的性质。
