Monnier V M, Stevens V J, Cerami A
J Exp Med. 1979 Nov 1;150(5):1098-107. doi: 10.1084/jem.150.5.1098.
The formation of sugar-cataracts has been hypothesized to involve the nonenzymatic glycosylation, sulfhydryl oxidation, and aggregation of lens proteins. Cataractous lenses of diabetic and galactosemic rats were analyzed for glycosylated lysine residues in crystallins. A five- and a ten-fold increase in glycosylated lysine residues was measured in galactose and diabetic cataracts, respectively. The modification was predominant in the insoluble fraction of the lens homogenate. The proteins were further examined for the presence of disulfide bonds and high molecular weight aggregates. After careful disruption of the lens in a nitrogen environment, a cloudy solution was obtained from cataractous lenses whereas a clear solution was obtained from normal lenses. The absorbance at 550 nm of the solution of both the galactosemic and the diabetic cataracts could be decreased by approximately 50% with the addition of dithioerythritol (50 mM). The presence of high molecular weight aggregates was ascertained by sucrose gradient centrifugation and gel filtration chromatography. The proteins were heterogenous in size and showed a mol wt range of 36 to greater than 176 million daltons. Treatment with dithioerythritol induced a marked decrease in the amount of high molecular weight proteins. These data suggest that sugar cataracts of experimental animals have, in common with human cataracts, the presence of high molecular weight aggregates which are in part linked by disulfide bonds.
糖性白内障的形成被认为涉及晶状体蛋白的非酶糖基化、巯基氧化和聚集。分析了糖尿病和半乳糖血症大鼠的白内障晶状体中晶状体蛋白的糖基化赖氨酸残基。在半乳糖性和糖尿病性白内障中，分别检测到糖基化赖氨酸残基增加了5倍和10倍。这种修饰在晶状体匀浆的不溶性部分中占主导地位。进一步检测了蛋白质中二硫键和高分子量聚集体的存在。在氮气环境中小心地破坏晶状体后，白内障晶状体得到浑浊溶液，而正常晶状体得到清澈溶液。加入二硫苏糖醇（50 mM）后，半乳糖血症和糖尿病性白内障溶液在550 nm处的吸光度可降低约50%。通过蔗糖梯度离心和凝胶过滤色谱法确定了高分子量聚集体的存在。这些蛋白质大小不均一，分子量范围为36至大于1.76亿道尔顿。用二硫苏糖醇处理导致高分子量蛋白质的量显著减少。这些数据表明，实验动物的糖性白内障与人类白内障一样，存在部分由二硫键连接的高分子量聚集体。
