Contribution of ubiquitous calpains to cataractogenesis in the spontaneous diabetic WBN/Kob rat
Contribution of ubiquitous calpains to cataractogenesis in the spontaneous diabetic WBN/Kob rat
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DOI：
10.1006/exer.2002.2065
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发表时间：
2002-11-01
影响因子：
3.4
通讯作者：
Shearer, TR
中科院分区：
文献类型：
--
作者：
Sakamoto-Mizutani, K;Fukiage, C;Shearer, TR
为了确定钙蛋白酶在人类白内障发生中的作用，需要在老年动物模型中进行研究。老年雄性WBN/Kob大鼠自发发生白内障沿着严重、持续性糖尿病伴高血糖症和肾病。本实验的目的是提供一个生化机制的参与普遍存在的钙蛋白酶在白内障的WBN/Kob大鼠。检测血糖和尿糖以确诊糖尿病，并通过裂隙灯生物显微镜观察白内障。对几个年龄的WBN/Kob和Wistar大鼠的透镜样品进行钙测定。进行酪蛋白酶谱、α-血影蛋白、钙蛋白酶2和钙蛋白酶10的免疫印迹分析以检测透镜样品中钙蛋白酶的活化。在1年内，雄性WBN/Kob大鼠的血清葡萄糖水平升高，并出现皮质性白内障，表明糖尿病性白内障。白内障伴随着钙蛋白酶激活的几个假定的生化指标，包括钙增加，α-血影蛋白的蛋白水解，和钙蛋白酶的酪蛋白水解活性降低，表明钙蛋白酶激活后自溶降解。普遍存在的钙蛋白酶激活可能参与自发性糖尿病WBN/Kob大鼠白内障形成的生化机制。WBN/Kob模型可能有助于阐明calpain 2和calpain 10在人类白内障发生中的作用。(C)2002年由Elsevier Science Ltd.出版
To determine the involvement of calpains in human cataractogenesis, studies in aged animal models are needed. Aged, male WBN/Kob rats spontaneously develop cataract along with severe, persistent diabetes with hyperglycemia and nephropathy. The purpose of present experiments was to provide a biochemical mechanism for the involvement of ubiquitous calpains in cataractogenesis in WBN/Kob rats. Serum and urinary glucose were measured to confirm diabetes, and cataracts were observed by slit lamp biomicroscopy. Calcium determinations were performed on lens samples from several ages of WBN/Kob and Wistar rats. Casein zymography, immunoblot analysis for alpha-spectrin, calpain 2, and calpain 10 were performed to detect activation of calpain in lens samples. Serum glucose levels increased and cortical cataract developed in male WBN/Kob rats within 1 year, indicating diabetic cataract. Cataract was accompanied by several presumptive biochemical indicators of calpain activation, including increased calcium, proteolysis of alpha-spectrin, and decreased caseinolytic activity for calpains suggesting calpain activation followed by autolytic degradation. Activation of ubiquitous calpains may contribute to biochemical mechanism of cataractogenesis in spontaneously diabetic WBN/Kob rats. The WBN/Kob model may be useful for elucidating the roles of calpain 2 and calpain 10 in human cataractogenesis. (C) 2002 Published by Elsevier Science Ltd.