高相对分子质量α-晶体蛋白分子伴侣活性在年龄相关性白内障中的变化  

Change of molecular chaperone activity of high-molecular-weight alpha-crystallin in age-related cataract

作　　者：严宏[1] 惠延年[2] 王建伟[1] 王永强[1] 丁正华[1] 郭勇[1] 

机构地区：[1]第四军医大学唐都医院眼科,西安710038 [2]第四军医大学西京医院眼科,西安710033

出　　处：《眼科研究》2006年第1期5-8,共4页Chinese Ophthalmic Research

基　　金：中国人民解放军总后勤部留学回国人员基金资助(97H26)

摘　　要：目的研究年龄相关性白内障高相对分子质量α晶体蛋白(αH晶体蛋白)的分子伴侣功能。方法101只白内障晶状体取自年龄相关性白内障(ARC)患者眼,26只透明晶状体取自意外死亡的健康青壮年角膜移植供体眼,使用SephacrylS300HR分离透明和混浊晶状体皮质和核αH晶体蛋白。采用αH晶体蛋白抑制过氧化氢酶(CAT)、βL晶体蛋白的热凝聚,以及糖基化和加热诱导CAT的失活作为分子伴侣的观察指标。结果年龄相关性白内障晶状体含大量αH晶体蛋白,αH晶体蛋白的作用较αL晶体蛋白弱,对CAT和βL晶体蛋白热凝聚的抑制作用相似。透明晶状体与ARC、65岁以上组与65岁以下组、Ⅱ级与Ⅳ级核之间αH晶体蛋白分子伴侣功能差异具显著性。αH晶体蛋白可保护果糖和加热诱导CAT的失活。结论人αH晶体蛋白具有分子伴侣活性。但活性较αL晶体蛋白低。晶状体在老化过程中受翻译后修饰(PTM)的严重影响,形成大量αH晶体蛋白聚合物,导致分子伴侣功能下降,可能是白内障发病的关键因素之一。Objective To evaluate the change of the molecular chaperone activity of high-molecular-weight alpha-crystallin （αH-crystallin） in age-related cataract （ARC）. Methods One hundred and one cataract lenses were obtained from age-relatedcataract patients during the operation and 26 clear lenses were obtained from corneal transplantation donators, αH-Crystallin of cortex and nucleus from human clear lens （ donor eyes） and cataractous lenses were separated by chromatography on Sephacryl S-300HR. The protection of αH-crystallin against thermal aggregation of catalase and βL-crystallin,inactivation of catalase by fructose and heat stress were measured spectrophotometrically. Results In age-related cataract and cataractous lens, a large amount of αH- crystallin was observed. The chaperone activity of α-crystallin was less than that of αL-crystallin （ approximately from 8%-26% ） （P〈0.01）. The prevention of αL-crystallin against thermal aggregation of catalase was similar to βL-crystallin （approximately from 16%-30% ）. There were significant difference in chaperone activity of αH-crystallin between transparent lenses and ARC lenses （approximately 24%-34% ）, 〉 65 years group and 〈 65 years group （approximately 3%-10%） ,Ⅱ nucleus group and Ⅳ nucleus group （approximately 4%-11% ） （P 〈 0.05）. αH-crystallin protected inactivation of catalase by fructose and heat stress. Conclusion Human αH-crystallin can function as a molecular chaperone, but the protective ability of αH-crystallin is lower than that of αH-crystallin. Post-translational modifications can introduce forming a large amount of αH-crystallin with aging,resulting in a reduction of chaperone-like activity. This may be a key factor in cataract formation.

关 键 词：αH-晶体蛋白 分子伴侣 年龄相关性白内障 翻译后修饰 

分 类 号：R776.1[医药卫生—眼科]