Reddy V N, Garadi R, Chakrapani B, Giblin F J
Eye Research Institute, Oakland University, Rochester, Mich.
Ophthalmic Res. 1988;20(3):191-9. doi: 10.1159/000266585.
The role of reduced glutathione (GSH) in lens membrane function was studied by depleting GSH with 1-chloro-2,4-dinitrobenzene (CDNB), a reaction catalyzed by GSH-S-transferase. Depletion of GSH in the lens epithelium by 70-90% led to a decrease in uptake and increase in efflux of 86Rb. ATP levels and Na+/K+-ATPase activity were normal while there was a slight decrease in lactate production. The results provide the first direct evidence that depletion of endogenous GSH per se does not lead to inactivation of Na+/K+-ATPase. However, lenses deficient in GSH when challenged with a normally tolerated level of H2O2 showed significant inactivation of membrane ATPase without a further increase in membrane permeability. Pretreatment with CDNB resulted in a 3-fold stimulation of the hexose monophosphate shunt activity which is attributed to the unexpected finding of a significant increase in the level of oxidized glutathione in the lens. It is concluded that deficiency of GSH causes a marked increase in membrane permeability and such lenses are susceptible to oxidative damage resulting in inactivation of the Na+/K+ pump, thus leading to ionic changes and cataract development.
通过用1-氯-2,4-二硝基苯（CDNB）消耗还原型谷胱甘肽（GSH）来研究其在晶状体膜功能中的作用，这一反应由谷胱甘肽-S-转移酶催化。晶状体上皮细胞中GSH消耗70 - 90%会导致86Rb摄取减少和流出增加。ATP水平和Na+/K+-ATP酶活性正常，而乳酸生成略有减少。结果首次直接证明内源性GSH的消耗本身不会导致Na+/K+-ATP酶失活。然而，当用正常耐受水平的H2O2攻击时，缺乏GSH的晶状体显示出膜ATP酶的显著失活，而膜通透性没有进一步增加。用CDNB预处理导致磷酸己糖支路活性提高3倍，这归因于晶状体中氧化型谷胱甘肽水平显著增加这一出乎意料的发现。得出的结论是，GSH缺乏会导致膜通透性显著增加，此类晶状体易受氧化损伤，导致Na+/K+泵失活，从而引发离子变化和白内障形成。
