ASCORBIC ACID GLYCATION AND SENILE CATARACT FORMATION

老年性白内障形成机制研究的首要目标 就是发现可以抑制或至少延缓 白内障形成的进展。如果这种病理可以推迟到 仅仅10年，这将消除大部分的白内障手术 每年演出一次。老年人晶状体增高症的分析 蛋白质的聚集和交联，这被认为是 白内障形成的基础。这些过程的化学作用， 然而，这在很大程度上仍是个未知数。 我们一直在研究抗坏血酸对晶状体蛋白质的修饰。 酸性糖基化，并发现了许多相似之处 体外糖化蛋白及老年人分离蛋白 隐形眼镜。晚期糖基化终产物的形成可能是 对晶状体的黄化或淡黄色负责，这一代 活性氧物种和蛋白质交联物的形成。这 工作一直受到阻碍，因为人们对这两个国家的情况知之甚少 尤其是抗坏血酸糖基化的化学或其结构 高级糖基化终产物和一般的交联物。在工作中 在这里，我们将通过不同的方法测量晶状体蛋白质的糖基化 抗坏血酸在生理条件下的分解产物 测定每种化合物在糖基化和交联过程中的活性。 特定氨基酸对之间的交联会被制备出来，并且它们的 测量稳定性并与目前存在的交联物的稳定性进行比较 在老化的人类晶状体的水不溶部分中。化学性质 几种抗坏血酸衍生的交联物将使用一种新的 模型多肽的分离方法。最后一点是， 通过抗坏血酸糖基化产生的增敏剂将与 老化的人体晶状体为特定的活性氧物种产生。

The primary goal of research on the mechanism of senile cataract formation is to discover treatments which can inhibit, or at least delay, the progression of cataract formation. If this pathology could be delayed by only 10 years, this would eliminate most of the cataract operations performed each year. Analysis of aged human lenses show increased aggregation and crosslinking of proteins, which are thought to be fundamental in cataract formation. The chemistry of these processes, however, remains largely unknown. We have been investigating the modification of lens proteins by ascorbic acid glycation, and have discovered a great number of similarities between in vitro glycated proteins and the proteins isolated from aged human lenses. The formation of advanced glycation endproducts may be responsible for the yellowing or brunescence of the lens, the generation of active oxygen species and the formation of protein crosslinks. This work has been hampered because so little is known about either the chemistry of ascorbic acid glycation in particular or the structure of advanced glycation endproducts and crosslinks in general. In the work proposed here we will measure the glycation of lens proteins by various ascorbic acid breakdown products under "physiological" conditions in order to determine the activity of each compound in glycation and crosslinking. Crosslinks between specific amino acid pairs will be prepared and their stability measured and compared to the stability of the crosslinks present in the water-insoluble fraction from aged human lens. The chemical nature of several ascorbate-derived crosslinks will be determined using a new isolation method with a model peptide. Finally, the nature of the sensitizers produced by ascorbate glycation will be compared to those in aged human lens for the specific active oxygen species produced.