Glutathione: A vital lens antioxidant
Glutathione: A vital lens antioxidant
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DOI：
10.1089/jop.2000.16.121
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发表时间：
2000-04-01
影响因子：
2.3
通讯作者：
Giblin, FJ
中科院分区：
文献类型：
--
作者：
Giblin, FJ
还原性化合物谷胱甘肽（GSH）在透镜中以异常高的浓度存在，它作为维持组织透明度的重要抗氧化剂发挥作用。结合位于透镜上皮和表层皮质中的活性谷胱甘肽氧化还原循环，GSH解毒潜在的破坏性氧化剂，如H2 O2和脱氢抗坏血酸。最近的研究表明，在透镜上皮细胞中，GSH具有重要的羟基自由基清除功能，而不依赖于细胞对H2 O2的解毒能力。GSH的消耗或氧化还原循环的抑制允许低水平的氧化剂损伤透镜上皮靶，例如Na/K-ATP酶、某些细胞骨架蛋白和与正常膜渗透性相关的蛋白。透镜核中的GSH水平相对较低，特别是在老化的透镜中，并且化合物如何从上皮细胞移动到器官的中心区域尚不清楚。最近，Sweeney等人证明了老年人晶状体中GSH迁移的皮质/核屏障。透镜核中GSH与蛋白-SH的相对低的比率，与该区域谷胱甘肽氧化还原循环的低活性相结合，使得核特别容易受到氧化应激的影响，如使用体内实验动物模型如高压氧，UVA光和谷胱甘肽过氧化物酶敲除小鼠。在这些模型中观察到的效应（目前正用于研究人老年性核性白内障的形成机制）包括透镜核二硫化物增加、核膜损伤和核光散射增加。需要开发治疗剂以减缓人透镜核中抗氧化活性的年龄相关损失，从而延迟白内障的发作。
The reducing compound glutathione (GSH) exists in an unusually high concentration in the lens where it functions as an essential antioxidant vital for maintenance of the tissue's transparency. In conjunction with an active glutathione redox cycle located in the lens epithelium and superficial cortex, GSH detoxifies potentially damaging oxidants such as H2O2 and dehydroascorbic acid. Recent studies have indicated an important hydroxyl radical-scavenging function for GSH in lens epithelial cells, independent of the cells' ability to detoxify H2O2. Depletion of GSH or inhibition of the redox cycle allows low levels of oxidant to damage lens epithelial targets such as Na/K-ATPase, certain cytoskeletal proteins and proteins associated with normal membrane permeability. The level of GSH in the nucleus of the lens is relatively low, particularly in the aging lens, and exactly how the compound travels from the epithelium to the central region of the organ is not known. Recently, a cortical/nuclear barrier to GSH migration in older human lenses was demonstrated by Sweeney et al. The relatively low ratio of GSH to protein -SH in the nucleus of the lens, combined with low activity of the glutathione redox cycle in this region, makes the nucleus especially vulnerable to oxidative stress, as has been demonstrated with use of in vivo experimental animal models such as hyperbaric oxygen, UVA light and the glutathione peroxidase knockout mouse. Effects observed in these models, which are currently being utilized to investigate the mechanism of formation of human senile nuclear cataract, include an increase in lens nuclear disulfide, damage to nuclear membranes and an increase in nuclear light scattering. A need exists for development of therapeutic agents to slow age-related loss of antioxidant activity in the nucleus of the human lens to delay the onset of cataract.