Biochemistry, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.
Biochemistry, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland; Departamento de Bioquímica y Biología Molecular, Universidad Complutense, Madrid, Spain.
Biophys J. 2019 Mar 19;116(6):1105-1114. doi: 10.1016/j.bpj.2019.02.002. Epub 2019 Feb 10.
The mode of interactions between palmitoyl lysophosphatidylcholine (palmitoyl lyso-PC) or other lysophospholipids (lyso-PLs) and palmitoyl ceramide (PCer) or other ceramide analogs in dioleoylphosphatidylcholine (DOPC) bilayers has been examined. PCer is known to segregate laterally into a ceramide-rich phase at concentrations that depend on the nature of the ceramides and the co-phospholipids. In DOPC bilayers, PCer forms a ceramide-rich phase at concentrations above 10 mol%. In the presence of 20 mol% palmitoyl lyso-PC in the DOPC bilayer, the lateral segregation of PCer was markedly facilitated (segregation at lower PCer concentrations). The thermostability of the PCer-rich phase in the presence of palmitoyl lyso-PC was also increased compared to that in the absence of palmitoyl lyso-PC. Other saturated lyso-PLs (e.g., palmitoyl lyso-phosphatidylethanolamine and lyso-sphingomyelin) also facilitated the lateral segregation of PCer in a similar manner as palmitoyl lyso-PC. When examined in the DOPC bilayer, it appeared that the association between palmitoyl lyso-PC and PCer was equimolar in nature. It is proposed that the interaction of PCer with lyso-PLs was driven by the need of ceramide to obtain a large-headgroup co-lipid, and saturated lyso-PLs were preferred co-lipids over DOPC because of the nature of their acyl chain. Structural analogs of PCer (1- or 3-deoxy-PCer) were also associated with palmitoyl lyso-PC, similarly to PCer, suggesting that the ceramide/lyso-PL interaction was not sensitive to structural alterations in the ceramide molecule. Binary complexes containing palmitoyl lyso-PC and ceramide were prepared, and these had a bilayer structure as ascertained by transmission electron microscopy. It is concluded that ceramides and lyso-PLs associated with each other both in binary bilayers and in ternary systems based on the DOPC bilayers. This association may have biological relevance under conditions in which both sphingomyelinases and phospholipase A enzymes are activated, such as during inflammatory processes.
已研究了棕榈酰溶血磷脂酰胆碱（棕榈酰溶血磷脂酰胆碱）或其他溶血磷脂（溶血磷脂）与棕榈酰神经酰胺（神经酰胺）或其他神经酰胺类似物在二油酰基磷脂酰胆碱（DOPC）双层中的相互作用模式。已知神经酰胺在浓度上会侧向分离到富含神经酰胺的相中，这取决于神经酰胺和共磷脂的性质。在 DOPC 双层中，神经酰胺在浓度高于 10mol％时形成富含神经酰胺的相。在 DOPC 双层中存在 20mol％棕榈酰溶血磷脂酰胆碱的情况下，神经酰胺的侧向分离明显得到促进（在较低的神经酰胺浓度下分离）。与不存在棕榈酰溶血磷脂酰胆碱时相比，存在棕榈酰溶血磷脂酰胆碱时富含神经酰胺的相的热稳定性也得到了提高。其他饱和溶血磷脂（例如，棕榈酰溶血磷脂酰乙醇胺和溶血鞘氨醇）也以类似于棕榈酰溶血磷脂酰胆碱的方式促进神经酰胺的侧向分离。在 DOPC 双层中检查时，似乎棕榈酰溶血磷脂酰胆碱与神经酰胺的缔合在本质上是等摩尔的。据推测，神经酰胺与溶血磷脂的相互作用是由神经酰胺获得大头部基团共脂质的需要驱动的，并且由于其酰链的性质，饱和溶血磷脂比 DOPC 更适合作为共脂质。神经酰胺的结构类似物（1-或 3-脱氧神经酰胺）也与棕榈酰溶血磷脂酰胆碱缔合，类似于神经酰胺，表明神经酰胺/溶血磷脂的相互作用对神经酰胺分子的结构改变不敏感。制备了含有棕榈酰溶血磷脂酰胆碱和神经酰胺的二元复合物，并且通过透射电子显微镜确定这些复合物具有双层结构。可以得出结论，神经酰胺和溶血磷脂在二元双层中和基于 DOPC 双层的三元系统中彼此缔合。这种缔合在同时激活鞘磷脂酶和磷脂酶 A 酶的情况下可能具有生物学相关性，例如在炎症过程中。
