Torrecillas Alejandro, Aroca-Aguilar J Daniel, Aranda Francisco J, Gajate Consuelo, Mollinedo Faustino, Corbalán-García Senena, de Godos Ana, Gómez-Fernández Juan C
Departamento de Bioquímica y Biología Molecular A, Facultad de Veterinaria, Universidad de Murcia, Apartado de Correos 4021, E-30080 Murcia, Spain.
Int J Pharm. 2006 Aug 2;318(1-2):28-40. doi: 10.1016/j.ijpharm.2006.03.008. Epub 2006 Mar 17.
The effect of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH(3), edelfosine), and six other analog asymmetric phosholipids on the physical properties of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) model membranes was studied using differential scanning calorimetry (DSC), (31)P-nuclear magnetic resonance ((31)P NMR) and X-ray diffraction. DSC data revealed that, at concentrations of 40mol% and higher, a new type of mixtures with higher T(c) and narrower transitions appeared with all the asymmetric lipids studied. At very high concentrations of these lipids (50-80 mol%), destabilization was observed in the systems probably because of the formation of micelles or small vesicles. In all cases, the asymmetric lipids at concentrations of 40 mol% induced the formation of interdigitated structures in the lamellar gel phase, as deduced from X-ray diffraction. The asymmetric phospholipids were also added to 1,2-dielaidoyl-sn-glycero-3-phosphoethanolamine (DEPE) model membranes and DSC data revealed that the lipids primarily affected transition from the lamellar gel (L(beta)) to the lamellar liquid crystalline (L(alpha)) phase in two aspects: the transition temperature was reduced, and the transition itself became broader and smaller. The lamellar liquid crystalline (L(alpha)) to inverted hexagonal phase (H(II)) transition was also affected, as detected by DSC and (31)P NMR data. Increasing concentrations of the asymmetric lipids reduced the formation of inverted hexagonal phases, which were completely inhibited in the case of ET-18-OCH(3). Since these compounds have been shown to have important biological actions through the plasma membrane, these results may help to understand the mechanism of action of these compounds. In addition these asymmetric lipids were tested for their capacity to induce cell apoptosis, and only ET-18-OCH(3) was found to have a clear effect, thus suggesting that the apoptotic effect is not exerted through changes in the biophysical properties of model membranes.
利用差示扫描量热法（DSC）、³¹P核磁共振（³¹P NMR）和X射线衍射，研究了1-O-十八烷基-2-O-甲基-sn-甘油-3-磷酸胆碱（ET-18-OCH₃，依地福新）以及其他六种不对称磷脂类似物对1,2-二肉豆蔻酰-sn-甘油-3-磷酸胆碱（DMPC）模型膜物理性质的影响。DSC数据显示，在浓度为40mol%及更高时，所有研究的不对称脂质都会出现一种具有更高Tc且转变更窄的新型混合物。在这些脂质的非常高浓度（50 - 80 mol%）下，系统中观察到不稳定现象，这可能是由于胶束或小囊泡的形成。在所有情况下，从X射线衍射推断，浓度为40 mol%的不对称脂质会诱导层状凝胶相中叉指状结构的形成。还将不对称磷脂添加到1,2-二油酰-sn-甘油-3-磷酸乙醇胺（DEPE）模型膜中，DSC数据显示，这些脂质主要在两个方面影响从层状凝胶（Lβ）到层状液晶（Lα）相的转变：转变温度降低，并且转变本身变得更宽且更小。如DSC和³¹P NMR数据所检测，层状液晶（Lα）到反相六角相（H(II)）的转变也受到影响。不对称脂质浓度的增加会减少反相六角相的形成，在ET-18-OCH₃的情况下，这种形成被完全抑制。由于这些化合物已被证明通过质膜具有重要的生物学作用，这些结果可能有助于理解这些化合物的作用机制。此外，测试了这些不对称脂质诱导细胞凋亡的能力，结果发现只有ET-18-OCH₃具有明显效果，因此表明凋亡效应不是通过模型膜生物物理性质的变化来发挥的。
