SPECTROSCOPIC AND RELATED STUDIES ON LENS MEMBRANE LIPID

晶状体膜脂的光谱及相关研究

• 批准号: 6489790
• 负责人: DOUGLAS BORCHMAN
• 金额: $ 26.12万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6489790
• 关键词: Raman spectrometry; aging; calcium ion; cataract; cell membrane; cholesterol; circular dichroism; cornea opacity; high performance liquid chromatography; human tissue; infrared spectrometry; interferometry; intermolecular interaction; lens; light scattering; membrane activity; membrane lipids; membrane proteins; membrane reconstitution /synthesis; membrane structure; oxidative stress; protein structure; sphingolipids

Description (from abstract): The pronounced effects of aging on the levels of oxidation and composition of human lens membranes have been studied extensively in our research. Publications by the investigator and others indicate that plasma membranes from cataractous tissues exhibit higher levels of oxidation as well as elevated sphingomyelin and cholesterol contents. Yet, the specific molecular events that relate these alterations to the process of opacification or cataractogenesis remain unclear. As cataracts are formed, lens transparency is lost due primarily to light scattering. The thrust of this project is to assess, at the molecular level, the fundamental reasons for which changes in lens membranes may result in the enhancement of light scattering. Specifically, the investigator proposes to quantify the contribution of light scattering that results from the tighter packing of the hydrocarbon chains in membranes with increased oxidation levels and sphingolipid content. Secondly, he will test the possible enhancement of Mie and Rayleigh scattering due to greater binding efficiency of a-crystallin to deranged membranes. Thirdly, the relative arnount of light scattering caused by the increase in permeability of calcium ions will be explored. Calcium ions, among many mechanisms, could lead to the scattering of light by either binding to lipids via a structural or syncretic (excluding water) mechanism or by forming protein condensates. Finally, the formation of oxidized condensates containing lipids and a mixture of crystallins that may dislodge from the membrane network will be investigated. These aggregates may serve as focal opacities that increase the contribution of Mie scattering to the overall loss of transparency with age and cataract. The ability to monitor, simultaneously and in situ, light scattering levels along with lipid and protein structure will enable us to identify specific molecular alterations and estimate their contribution to the overall level of light scattering in cataractous tissues. An understanding of these alterations will facilitate the development of therapies to prevent or perhaps even reverse these changes.

描述（来自摘要）： 老化对氧化水平和组成的显著影响， 在我们的研究中已经广泛地研究了人类透镜膜。 研究者和其他人的出版物表明， 白内障组织表现出较高的氧化水平以及升高的 鞘磷脂和胆固醇含量。然而，特定的分子事件， 将这些改变与混浊或白内障形成过程联系起来 仍然不清楚。随着白内障的形成，透镜的透明度由于 主要是光散射。该项目的主旨是评估，在 分子水平，其根本原因是在透镜膜的变化 可导致光散射的增强。 具体来说，研究人员建议量化光的贡献， 由于烃链的紧密堆积而产生的散射， 膜具有增加的氧化水平和鞘脂含量。第二、 他将测试米氏和瑞利散射的可能增强， α-晶状体蛋白与紊乱的膜的结合效率更高。三是 由渗透性增加引起的光散射的相对数量 将探索钙离子。在许多机制中，钙离子可能会导致 光的散射，通过结合到脂质通过结构或 融合（不包括水）机制或通过形成蛋白质缩合物。 最后，形成含有脂质和混合物的氧化冷凝物， 可能从膜网络中脱落的晶体蛋白将被 研究了这些聚集体可作为局灶性混浊， 米氏散射对透明度随年龄的总体损失的贡献， 白内障同时和原位监测光散射的能力 水平沿着与脂质和蛋白质结构将使我们能够识别 特定的分子改变，并估计其对整体的贡献 白内障组织中的光散射水平。了解这些 这些改变将促进治疗的发展， 甚至逆转这些变化。