SPECTROSCOPIC AND RELATED STUDIES ON LENS MEMBRANE LIPID

晶状体膜脂的光谱及相关研究

• 批准号: 6342602
• 负责人: DOUGLAS BORCHMAN
• 金额: $ 25.37万
• 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/6342602
• 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(摘自摘要)： 老化对氧化水平和组成的显著影响 在我们的研究中，人们对晶状体膜进行了广泛的研究。 研究人员和其他人的出版物表明，来自 白内障组织表现出更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 将这些变化与混浊或白内障形成过程联系起来 目前仍不清楚。随着白内障的形成，晶状体透明度会因 主要是光散射。该项目的主旨是在 分子水平，晶状体膜变化的根本原因 可能会导致光散射的增强。 具体地说，研究人员建议量化光的贡献 由于碳氢链堆积更紧密而导致的分散 氧化水平和鞘磷脂含量增加的膜。第二， 他将测试Mie和Rayleigh散射的可能增强，原因是 A-晶状体蛋白与错乱的膜的结合效率更高。第三， 由渗透率增加引起的光散射的相对计数 我们将探索钙离子。在许多机制中，钙离子可能导致 通过结构上的或结构上的与脂类结合而使光散射 融合(不包括水)机制或通过形成蛋白质凝聚体。 最后，含有脂类和混合物的氧化冷凝物的形成 可能从膜网络中排出的晶体蛋白将是 调查过了。这些聚集体可以作为局灶性浑浊，从而增加 米氏散射对透明度随年龄和年龄的总体损失的贡献 白内障。同时、就地监测光散射的能力 水平以及脂肪和蛋白质结构将使我们能够识别 具体的分子变化，并估计它们对整体的贡献 白内障组织中的光散射水平。对这些的理解 改变将促进治疗方法的发展，以防止或可能 甚至逆转这些变化。