PROGRESSIVE CHANGES IN LENS CRYSTALLIN GLYCATION AND HIGH-MOLECULAR-WEIGHT AGGREGATE FORMATION LEADING TO CATARACT DEVELOPMENT IN STREPTOZOTOCIN-DIABETIC RATS
PROGRESSIVE CHANGES IN LENS CRYSTALLIN GLYCATION AND HIGH-MOLECULAR-WEIGHT AGGREGATE FORMATION LEADING TO CATARACT DEVELOPMENT IN STREPTOZOTOCIN-DIABETIC RATS
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DOI：
10.1016/s0014-4835(87)80011-8
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发表时间：
1987-02-01
影响因子：
3.4
通讯作者：
ABRAHAM, EC
中科院分区：
文献类型：
--
作者：
PERRY, RE;SWAMY, MS;ABRAHAM, EC
由于其显著的寿命，透镜晶体蛋白在糖尿病高血糖期间经历大量的糖化（非酶促糖基化）。这些翻译后修饰有可能破坏透镜晶体蛋白的结构和功能特性，并有助于白内障的形成。链脲佐菌素诱导的糖尿病大鼠用于研究透镜蛋白的糖基化和不溶性高分子量（HMW）聚集体的形成之间的关系，这些聚集体被认为是白内障形成的原因。糖尿病发作后，白内障在大约12至13周内发展。以这种方式对动物进行随访，直至发生白内障，并再随访63天。每3周处死5只对照大鼠和5只糖尿病大鼠，并摘除晶状体。通过亲和层析法检查每只动物晶状体中的糖化蛋白和糖化氨基酸水平。此外，通过分子筛HPLC技术监测晶状体蛋白组成的变化和HMW聚集体的形成。随着糖尿病性高血糖的持续，可溶性和可溶性组分中的糖化蛋白呈线性增加。该增加被可溶性HMW和不溶性HMW聚集体的增加所抵消。其他变化包括反应性巯基减少，表明二硫键形成增加。γ-在高血糖性白内障前期和白内障阶段，晶状体蛋白水平也以线性方式降低。透镜晶体蛋白的糖基化、活性巯基的消失和高分子量聚集体的形成是相互关联的。
Because of their remarkable longevity, lens crystallins undergo a substantial amount of glycation (non-enzymatic glycosylation) during diabetic hyperglycemia. These post-translational modifications have the potential to disrupt the structural and functional properties of the lens crystallins and contribute to the formation of cataracts. Streptozotocin-induced diabetic rats were used to study the relationship between glycation of lens proteins and the formation of insoluble high-molecular-weight (HMW) aggregates believed to be responsible for cataract formation. After the onset of diabetes, cataracts developed in about 12- to 13 weeks. The animals were followed in this manner until cataracts developed and for an additional 63 days. Five control and five diabetic rats were killed every 3 weeks and lenses removed. Levels of glycated protein and glycated amino acids in lenses from each animal were examined by affinity chromatography. In addition the changes in crystallin composition and development of HMW aggregates were monitored by molecular-sieve HPLC techniques. As diabetic hyperglycemia continued there was a linear increase in glycated protein in both the soluble and isoluble fractions. This increase was paralleled by an increase in the soluble HMW and insoluble HMW aggregates. Other changes included a decrease in reactive sulfhydryls which indicates an increase in disulfide bond formation. The .gamma.-crystallin levels also decreased in a linear fashion during the hyperglycemic pre-cataract and cataract stages. It appears that the glycation of lens crystallin, the disappareance of reactive sulfhydryls and the formation of HMW aggregates are interrelated.