Caspase activation in retinas of diabetic and galactosentic mice and diabetic patients
Caspase activation in retinas of diabetic and galactosentic mice and diabetic patients
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DOI：
10.2337/diabetes.51.4.1172
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发表时间：
2002-04-01
期刊：
影响因子：
7.7
通讯作者：
Kern, TS
中科院分区：
文献类型：
--
作者：
Mohr, S;Xi, X;Kern, TS
视网膜毛细血管细胞凋亡在糖尿病早期就开始，并可能导致毛细血管闭塞，这是糖尿病视网膜病变的一个重要特征。 Caspases是蛋白水解酶，与细胞凋亡的诱导和执行阶段密切相关，但其在糖尿病视网膜病变发展中的作用尚未被研究。我们的研究重点是测量不同糖尿病持续时间的小鼠视网膜中多种半胱天冬酶的活性。几种 caspase（包括 caspase-1、-2 -6、-8 和 -9）早在糖尿病 2 个月时就被激活。半胱天冬酶活性模式随着疾病持续时间的增加而变化，表明半胱天冬酶级联缓慢发展。糖尿病病程较长后，刽子手 caspase（例如 cas-6 和 -3）的活性升高，cas-3 活性的诱导与糖尿病病程相关，在糖尿病病程中，毛细血管细胞开始显示出凋亡的证据。 2 型糖尿病患者的视网膜同样显示 cas-1、-3、-4 和 -6 的活性显着增加。为了进行比较，还在实验性半乳糖血症（另一种发展为糖尿病样视网膜病变的模型）中测量了视网膜半胱天冬酶。糖尿病和半乳糖血症之间的 caspase 激活模式不同，但两者的血液己糖浓度升高后，cas-1 活性很快升高。半胱天冬酶提供了新的治疗靶点来测试细胞凋亡在糖尿病视网膜病变发展中的作用。
Apoptosis of retinal capillary cells begins early in diabetes and likely contributes to the capillary obliteration that is an important feature of diabetic retinopathy. Caspases are proteolytic enzymes that are closely involved in the induction and execution phases of apoptosis, but their role in the development of diabetic retinopathy has not been studied previously. Our study focused on the measurement of activities of multiple caspases in retinas of mice at different durations of diabetes. Several caspases (including caspases-1, -2 -6, -8, and -9) were activated as early as 2 months of diabetes. The caspases activity pattern changed with increasing duration of disease, suggesting a slowly developing caspases cascade. Activities of executioner caspases (e.g., cas-6 and -3) became elevated after longer duration of diabetes, and the induction of cas-3 activity was associated with the duration of diabetes at which capillary cells begin to show evidence of undergoing apoptosis. Retinas from patients with type 2 diabetes likewise showed a significant increase in activities of cas-1, -3, -4, and -6. For comparison, retinal caspases were also measured in experimental galactosemia, another model that develops a diabetic-like retinopathy. The pattern of caspases activation differed between diabetes and galactosemia, but cas-1 activity became elevated soon after elevation of blood hexose concentration in both. Caspases offer new therapeutic targets to test the role of apoptosis in the development of diabetic retinopathy.