LENS INHIBITOR PROTEINS AND CATARACTOGENESIS

许多研究人员认为，阳光（特别是UV-B） 白内障的形成。 UV-B已被确定为一种风险 流行病学研究中的白内障因素，以及 体外照射晶状体或透镜晶状体蛋白支持光- 蛋白质损伤的氧化机制。 紫外光损伤的许多特点， 然而，体外，与已知的老年或 褐发性白内障 这些相互矛盾的意见在本 格兰特，并提出了一个新的假说，紫外线和氧化损伤。 这 涉及到蛋白质只在 构成透镜中的水不溶性部分的超聚集体 原子核 这允许氧化化学在受保护的环境中进行。 非极性环境。 将采取几种不同的方法， 通过实现以下具体目标来证明这一假设： 1)确定水不溶性的结构和聚集状态 牛和人晶状体的部分。 2)比较天然α-晶状体蛋白和α-晶状体蛋白的UV诱导的氧化， 晶体蛋白在超聚集体中的存在和不存在体内水平的 保护剂 还建议对蛋白质水解进行研究，并将继续进行 透镜蛋白酶和抑制剂的表征。 这将包括： 1)继续研究天然和聚集的α-晶体蛋白的作用 作为蛋白水解酶的抑制剂。 2)一种新的透镜弹性蛋白酶的特性鉴定和一种新的晶状体弹性蛋白酶的启动 寻找催化α-葡聚糖的内源性裂解的酶， 晶体蛋白

Many investigators have suggested a role for sunlight (specifically UV-B light) in the formation of cataract. UV-B has been identified as a risk factor for cataract in epidemiology studies, and laboratory data on the irradiation of lenses or lens crystallins in vitro supports a photo- oxidative mechanism for protein damage. Many features of UV photodamage in vitro, however, are inconsistent with what is known about senile or brunescent cataract. These conflicting observations are addressed in this grant, and a new hypothesis for UV and oxidative damage is presented. This involves the idea that proteins are modified solely within the confines of the super-aggregates which make up the water-insoluble fraction in the lens nucleus. This permits oxidative chemistry to be carried out in a protected and nonpolar environment. Several different approaches will be taken to prove this hypothesis by carrying out the following specific aims: 1) Determine the structure and aggregate state of the water-insoluble fraction from bovine and human lenses. 2) Compare the UV-induced oxidation of native alpha-crystallin and alpha- crystallin in super-aggregates both with and without in vivo levels of protective agents. Studies are also proposed on proteolysis, and will continue the characterization of lens proteases and inhibitors. This will include: 1) Continued studies on the role of native and aggregated alpha-crystallins as inhibitors of proteolytic enzymes. 2) Characterization of a new lens elastase enzyme, and the initiation of a search for the enzyme(s) which catalyze the endogenous cleavage of alpha- crystallin.