Fluorescence Studies Of Polyunsaturated Phospholipids

神经元和视网膜组织富含含有一个或两个长链多不饱和酰基链的磷脂。这些研究旨在确定含有多不饱和酰基链的磷脂调节G蛋白偶联受体信号的分子基础，特别是22:6n-3。研究还集中在这些磷脂对急性暴露于乙醇的反应。荧光能量转移（FRET）研究表明，在含有di16:0和di22:6 PCs加上胆固醇的双分子层中，横向结构域的形成依赖于胆固醇和视紫红质的存在。横向结构域形成在22:6n-3含脂双分子层中的作用正在进一步研究中。酰基链自由体积和曲率应力都被认为是调节膜蛋白功能的双层性质。实验表明，这两种性质之间存在反比关系，表明它们在调节蛋白质功能方面可能具有相反的作用。最近的研究表明胆固醇分布的横向异质性是生物膜结构域形成的驱动力。为了确定磷脂组成在这些结构域形成中的作用，研究了胆固醇划分为确定的脂质组成的双层。提出了一种测量胆固醇分配到脂质双分子层的新方法。这些研究表明胆固醇的分配是由磷脂头基团和酰基链组成决定的。多不饱和酰基链在降低脂质膜胆固醇水平方面是最有效的，而反式脂肪酸则会增加膜胆固醇含量。这些研究对于开发和理解22:6n-3酰基链在结构域形成、膜蛋白功能调节以及与多不饱和脂肪酸和反式脂肪酸相关的健康益处和缺陷中的作用具有重要意义。

Neuronal and retinal tissues are high in phospholipids containing one or two long chain polyunsaturated acyl chains. These studies are directed towards determining a molecular basis for the modulation of G protein-coupled receptor signaling by phospholipids containing polyunsaturated acyl chains, in particular 22:6n-3. Studies are also focused on the response of these phospholipids to the acute exposure to ethanol. Fluorescence Energy Transfer (FRET) studies have demonstrated lateral domain formation in bilayers containing di16:0 and di22:6 PCs plus cholesterol, which was dependent on the presence of both cholesterol and rhodopsin. The role of lateral domain formation in bilayers of 22:6n-3 containing lipids is being further investigated. Both acyl chain free volume and curvature stress have been invoked as bilayer properties, which modulate membrane protein function. Experiments indicate an inverse relationship between these two properties, suggesting that they may have opposite effects with respect to modulating protein function. Recent studies have implicated lateral heterogeneity in cholesterol distribution as a driving force for domain formation in biological membranes. In order to determine the role of phospholipid composition in the formation of these domains, the partitioning of cholesterol into bilayers of defined lipid composition was studied. A novel method of measuring cholesterol partitioning into lipid bilayers was developed. These studies indicate that cholesterol partitioning is determined by both phospholipid head group and acyl chain composition. Polyunsaturated acyl chains are among the most effective in reducing the level of cholesterol in lipid membranes, while trans fatty acids increase membrane cholesterol content. These studies are important in developing and understanding the role of 22:6n-3 acyl chains in domain formation, the modulation of membrane protein function, and the health benefits and deficits associated with polyunsaturated fatty acids and trans fatty acids, respectively.