Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA.
Biomolecules. 2020 Oct 7;10(10):1418. doi: 10.3390/biom10101418.
Cataracts of many different etiologies are associated with oxidation of lens components. The lens is protected by maintenance of a pool of reduced glutathione (GSH) and other antioxidants. Because gap junction channels made of the lens connexins, Cx46 and Cx50, are permeable to GSH, we tested whether mice expressing two different mutants, Cx46fs380 and Cx50D47A, cause cataracts by impairing lens glutathione metabolism and facilitating oxidative damage. Levels of GSH were not reduced in homogenates of whole mutant lenses. Oxidized glutathione (GSSG) and the GSSG/GSH ratio were increased in whole lenses of Cx50D47A, but not Cx46fs380 mice. The GSSG/GSH ratio was increased in the lens nucleus (but not cortex) of Cx46fs380 mice at 4.5 months of age, but it was not altered in younger animals. Carbonylated proteins were increased in Cx50D47A, but not Cx46fs380 lenses. Thus, both mouse lines have oxidizing lens environments, but oxidative modification is greater in Cx50D47A than in Cx46fs380 mice. The results suggest that GSH permeation through lens connexin channels is not a critical early event in cataract formation in these mice. Moreover, because oxidative damage was only detected in animals with significant cataracts, it cannot be an early event in their cataractogenesis.
许多不同病因的白内障与晶状体成分的氧化有关。晶状体通过维持还原型谷胱甘肽 (GSH) 和其他抗氧化剂的储备来得到保护。由于由晶状体连接蛋白 Cx46 和 Cx50 组成的间隙连接通道可通透 GSH，我们检测了表达两种不同突变体（Cx46fs380 和 Cx50D47A）的小鼠是否通过损害晶状体谷胱甘肽代谢和促进氧化损伤而导致白内障。整个突变体晶状体匀浆中的 GSH 水平没有降低。整个 Cx50D47A 晶状体中的氧化型谷胱甘肽 (GSSG) 和 GSSG/GSH 比值增加，但 Cx46fs380 小鼠则没有。在 4.5 个月大的 Cx46fs380 小鼠的晶状体核（而非皮质）中，GSSG/GSH 比值增加，但在较年轻的动物中并未改变。Cx50D47A 晶状体中的羰基化蛋白增加，但 Cx46fs380 晶状体则没有。因此，两种小鼠品系都有氧化的晶状体环境，但 Cx50D47A 中的氧化修饰比 Cx46fs380 小鼠更为严重。结果表明，GSH 通过晶状体连接蛋白通道通透不是这些小鼠白内障形成的早期关键事件。此外，由于仅在有明显白内障的动物中检测到氧化损伤，因此它不可能是白内障形成的早期事件。
