MAILLARD REACTIONS AND OXIDATION IN CATARACTOGENESIS

描述：已经提出了几种机制来解释 白内障形成过程中发生的生化变化。 其中有 活性氧（ROS）和非酶的氧化损伤 晶状体蛋白的糖基化（美拉德反应）。 美拉德反应， 晶体蛋白上的氨基和糖之间的反应， 通过缩合产物，Amadori产物，其通过随后的 反应形成了结构多样的化合物， 晚期糖基化终产物（AGEs）。 阿马多利人的存在 在透镜中已经确定了产品以及特定AGEs。 几 最近的研究表明，糖化蛋白可以产生ROS。 是 可以想象的是，糖化晶体蛋白可以作为ROS的来源， 透镜并诱导氧化损伤。 在白内障形成期间，透镜 谷胱甘肽水平显著降低。 这可能会导致 抗氧化潜力和降低的谷胱甘肽酶活性， 将甲基乙二醛（MG）转化为D-乳酸。 因此，MG可能会累积 并通过AGE形成诱导蛋白质损伤。 MG也可以产生于 糖和抗坏血酸的自氧化。 大量的MG是 据报道存在于人类透镜中。 主要研究者 最近证实MG可与透镜晶体蛋白快速反应， 形成能够交联蛋白质并产生荧光蛋白的AGEs 加合物 因此，首席研究员假设， 美拉德反应引起的ROS和AGEs可能对透镜造成附带损害 晶状体蛋白在白内障发生中的作用 在这份报告中，校长 研究者计划通过体外和体内试验检验这一假设 实验 主要目标包括：（1）展示 由糖化晶体蛋白形成活性氧， 确定影响其形成的因素;（2） 物理参数的特定修改和变化的测定 在晶状体蛋白中由美拉德反应产物产生的ROS;（3） 测定美拉德反应诱导的氧化 器官培养透镜混浊和白内障形成的改良 （4）确定实验动物之间的关系 MG介导的美拉德反应和氧化在白内障形成中的作用 特异性探针和新型抗体。 本文中概述的实验 预计这些建议将使人们更好地了解 白内障形成中的透镜蛋白质修饰。

DESCRIPTION: Several mechanisms have been put forward to explain the biochemical changes that occur in cataract formation. Among them are the oxidative damage by reactive oxygen species (ROS) and non-enzymatic glycosylation (Maillard reaction) of crystallins. The Maillard reaction, the reaction between amino groups on crystallins and sugars, proceeds through a condensation product, the Amadori product, which by subsequent reactions forms structurally diverse compounds that are collectively known as advanced glycation end products (AGEs). The presence of the Amadori product as well as specific AGEs have been established in the lens. Several recent studies have shown that glycated proteins can generate ROS. It is conceivable that glycated crystallins may function as a source of ROS in the lens and induce oxidative damage. During cataract formation, the lens glutathione level decreases significantly. This may lead to a decrease in the antioxidant potential and diminished activity of glyoxalase, that converts methylglyoxal (MG) to D-lactate. As a result, MG may accumulate and induce protein damage through AGE formation. MG can also arise from autoxidation of sugars and ascorbate. Significant amounts of MG are reported to be present in the human lens. The principal investigator has recently demonstrated that MG can rapidly react with lens crystallins to form AGEs that can crosslink proteins and generate fluorescent protein adducts. The principal investigator therefore hypothesizes that formation of ROS and AGEs by the Maillard reaction may cause collateral damage to lens crystallins in cataractogenesis. In this proposal, the principal investigator plans to test this hypothesis by in vitro and in vivo experiments. The major objectives include (1) demonstration of the formation of reactive oxygen species by glycated crystallins and determination of the factors which influence their formation; (2) determination of specific modifications and changes in physical parameters in crystallins by ROS generated from the Maillard reaction products; (3) determination of the effects of Maillard reaction-induced oxidative modifications on lens opacity and cataract formation in organ cultured lens and experimental animals and (4) determination of relationship(s) between MG-mediated Maillard reactions and oxidation in cataract formation using specific probes and a novel antibody. The experiments outlined in this proposal are expected to provide a better understanding of the mechanisms of lens protein modifications in cataract formation.