Fluorescence Studies Of Polyunsaturated Phospholipids

多不饱和磷脂的荧光研究

• 批准号: 6508249
• 负责人: Burton J Litman
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6508249
• 关键词: G protein; biological signal transduction; biophysics; calorimetry; chemical models; chemical structure function; ethanol; fluorescence; fluorescence resonance energy transfer; fluorescent dye /probe; lipid bilayer membrane; long chain fatty acid; membrane activity; membrane lipids; membrane structure; phase change; phosphatidylcholines; phospholipids; retina; synaptosomes; unsaturated fatty acids

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.

神经元和视网膜组织中含有大量含有一个或两个长链多不饱和酰基链的磷脂。这些研究是针对确定由含有多不饱和酰基链，特别是22：6 n-3的磷脂调节G蛋白偶联受体信号传导的分子基础。研究还集中在这些磷脂对急性暴露于乙醇的反应上。荧光能量转移（FRET）研究已经证明了在含有di 16：0和di 22：6 PC加胆固醇的双层中横向结构域的形成，这依赖于胆固醇和视紫红质两者的存在。侧域形成的22：6 n-3含有脂质的双层的作用正在进一步研究。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，这两个属性之间的反比关系，这表明他们可能有相反的影响，相对于调节蛋白质的功能。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，研究了胆固醇分配到确定的脂质组成的双层中。建立了一种测定胆固醇在脂质双层中分配的新方法。这些研究表明，胆固醇分配是由磷脂头基和酰基链组成。多不饱和酰基链在降低脂质膜中胆固醇水平方面是最有效的，而反式脂肪酸增加膜胆固醇含量。这些研究对于开发和理解22：6 n-3酰基链在结构域形成、膜蛋白功能调节以及分别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非常重要。