Endoplasmic reticulum stress induces retinal endothelial permeability of extracellular-superoxide dismutase
Endoplasmic reticulum stress induces retinal endothelial permeability of extracellular-superoxide dismutase
复制标题
DOI：
10.3109/10715762.2011.595408
复制
发表时间：
2011-09-01
影响因子：
3.3
通讯作者：
Ikeda, Tsunehiko
中科院分区：
文献类型：
--
作者：
Adachi, Tetsuo;Yasuda, Hiroyuki;Ikeda, Tsunehiko
本研究旨在通过探究两种可能性来确定增殖性糖尿病视网膜病变患者玻璃体内细胞外超氧化物歧化酶（EC - SOD）水平升高的原因：第一，视网膜中EC - SOD表达的变化；第二，由于内质网应激参与糖尿病视网膜病变中的血管损伤，使用内质网应激诱导剂处理后EC - SOD通过内皮单层渗漏。在小鼠玻璃体内注射衣霉素增加了示踪染料穿过视网膜血管的通透性，而视网膜EC - SOD mRNA水平未发生变化。使用毒胡萝卜素或衣霉素处理可使EC - SOD通过视网膜内皮细胞层的渗漏增加。使用内质网应激诱导剂处理可使紧密连接蛋白 - 5的表达显著降低。使用化学伴侣4 - 苯基丁酸预处理内皮细胞可显著抑制这些现象。我们的观察结果表明，内质网应激导致紧密连接蛋白中紧密连接蛋白 - 5的下调，并可能诱导内皮通透性升高以及EC - SOD渗漏到玻璃体中。
The aim of this study was to determine the reasons why the intravitreal level of extracellular-superoxide dismutase (EC-SOD) increases in proliferative diabetic retinopathy patients by the investigation of two possibilities: first, change of EC-SOD expression in the retina; and secondly, leakage of EC-SOD through the endothelial monolayer by the treatment with endoplasmic reticulum (ER) stress inducers because ER stress is known to be involved in the vascular impairment in diabetic retinopathy. Intravitreous injection of tunicamycin in mice increased the permeability of tracer dye across retinal blood vessels while the retinal EC-SOD mRNA level was not changed. The leakage of EC-SOD through the retinal endothelial cell layer was elevated by the treatment with thapsigargin or tunicamycin. The expression of claudin-5 was significantly decreased by the treatment with the ER stress inducers. These phenomena were significantly suppressed by the pretreatment of endothelial cells with a chemical chaperone 4-phenylbutyric acid. Our observations suggest that ER stress leads to the down-regulation of claudin-5 among tight junction proteins and may induce the elevation of endothelial permeability and leakage of EC-SOD into the vitreous body.