Centro de Quimica e Bioquimica, DQB, Faculdade de Ciências da Universidade de Lisboa , Campo Grande, Ed. C8, 1749-016 Lisboa Portugal.
Langmuir. 2014 Mar 4;30(8):2117-28. doi: 10.1021/la403977f. Epub 2014 Feb 17.
Recent research regarding 2-hydroxylated fatty acids (2OHFAs) showed clear evidence of their benefits in the treatment of cancer, inflammation, and neurodegenerative disorders such as Alzheimer's disease. Monolayer compressibility isotherms and isothermal titration calorimetry of 2OHFA (C18-C22) in phosphatidylcholine/phosphatidylethanolamine/sphingomyelin/cholesterol (1:1:1:1 mole ratio), a mixture that mimics the composition of mammalian plasma membrane, were performed to assess the membrane binding capacity of 2OHFAs and their natural, nonhydroxylated counterparts. The results show that 2OHFAs are surface-active substances that bind membranes through exothermic, spontaneous processes. The main effects of 2OHFAs are a decrease in lipid order, with a looser packing of the acyl chains, and a decreased dipole potential, regardless of the 2OHFAs' relative affinity for the lipid bilayer. The strongest effects are usually observed for 2-hydroxyarachidonic (C20:4) acid, and the weakest one, for 2-hydroxydocosahexaenoic acid (C22:6). In addition, 2OHFAs cause increased hydration, except in gel-phase membranes, which can be explained by the 2OHFA preference for membrane defects. Concerning the membrane dipole potential, the magnitude of the reduction induced by 2OHFAs was particularly marked in the liquid-ordered (lo) phase (cholesterol/sphingomyelin-rich) membranes, those where order reduction was the smallest, suggesting a disruption of cholesterol-sphingolipid interactions that are responsible for the large dipole potential in those membranes. Moreover, 2OHFA effects were larger than for both lo and ld phases separately in model membranes with liquid disordered (ld)/lo coexistence when both phases were present in significant amounts, possibly because of the facilitating effect of ld/lo domain interfaces. The specific and marked changes induced by 2OHFAs in several membrane properties suggest that the initial interaction with the membrane and subsequent reorganization might constitute an important step in their mechanisms of action.
最近关于 2-羟基脂肪酸（2OHFAs）的研究表明，它们在治疗癌症、炎症和神经退行性疾病（如阿尔茨海默病）方面具有明显的益处。在磷脂酰胆碱/磷脂酰乙醇胺/鞘磷脂/胆固醇（1:1:1:1 摩尔比）的混合物中进行了 2OHFA（C18-C22）的单层可压缩性等温线和等温滴定量热法，该混合物模拟了哺乳动物质膜的组成，以评估 2OHFAs 及其天然非羟基化对应物的膜结合能力。结果表明，2OHFAs 是通过放热、自发过程结合膜的表面活性剂。2OHFAs 的主要作用是降低脂质有序性，使酰基链的堆积更松散，并降低偶极电位，而与 2OHFAs 对脂质双层的相对亲和力无关。最强的作用通常观察到 2-羟基花生四烯酸（C20:4）酸，最弱的作用观察到 2-羟基二十二碳六烯酸（C22:6）。此外，除凝胶相膜外，2OHFAs 还会导致水合增加，这可以用 2OHFA 对膜缺陷的偏好来解释。关于膜偶极电位，2OHFAs 引起的降低幅度在富含胆固醇/鞘磷脂的有序（lo）相（有序相）膜中尤为明显，在这些膜中，有序相的降低幅度最小，这表明胆固醇-鞘磷脂相互作用被破坏，这是这些膜中偶极电位较大的原因。此外，在含有大量无序相（ld）/lo 共存的模型膜中，2OHFA 的作用大于 lo 和 ld 相分别的作用，这可能是因为无序相/lo 域界面的促进作用。2OHFAs 在几种膜性质中引起的特异性和明显变化表明，与膜的初始相互作用和随后的重组可能是其作用机制中的重要步骤。
