Lou Marjorie F
Redox Biology Center, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
Prog Retin Eye Res. 2003 Sep;22(5):657-82. doi: 10.1016/s1350-9462(03)00050-8.
The high content of glutathione (GSH) in the lens is believed to protect thiols in structural proteins and enzymes for proper biological functions. The lens has both biosynthetic and regenerating systems for GSH to maintain its large pool size. However, ageing lenses or lenses under oxidative stress show an extensively diminished size of GSH pool with some protein thiols being S-thiolated by oxidized non-protein thiols to form protein-thiol mixed disulfides, either as protein-S-S-glutathione (PSSG) or protein-S-S-cysteine (PSSC) or protein-S-S-gamma-glutamylcysteine. It was shown in an H(2)O(2)-induced cataract model that PSSG formation precedes a cascade of events before cataract formation, starting with protein disulfide crosslinks, protein solubility loss and high molecular weight aggregation. Furthermore, this early oxidative damage in protein thiols can be spontaneously reversed in H(2)O(2) pretreated lenses if the oxidant is removed in time. This dethiolation process appears to have mediated through a redox-regulating enzyme, thioltransferase (TTase), which is ubiquitously present in microbial, plant and animal tissues, including the lens. The GSH-dependent, low molecular weight (11.8 kDa) cytosolic enzyme plays an important role in oxidative defense and can modulate key metabolic enzymes in the glycolytic pathway. The enzyme repairs oxidatively damaged proteins/enzymes through its unique catalytic site with a vicinal cysteine moiety, which can specifically dethiolate protein-S-S-glutathione and restore protein free SH groups for proper enzymatic or protein functions. Most importantly, it has been demonstrated that thioltransferase has a remarkable resistance to oxidation (H(2)O(2)) in cultured human and rabbit lens epithelial cells under oxidative stress conditions when other oxidation defense systems of GSH peroxidase and GSH reductase are severely inactivated. A second repair enzyme, thioredoxin (TRx), which is NADPH-dependent, is widely found in many lower and higher life forms of life. It can dethiolate protein disulfides and thus is an extremely important regulator for redox homeostasis in the cells. Thioredoxin has been recently found in the lens and has been shown to participate in the repair process of oxidatively damaged lens proteins/enzymes. These two enzymes may work synergistically to regulate and repair thiols in lens proteins and enzymes, keeping a balanced redox potential to maintain the function of the lens.
晶状体中高含量的谷胱甘肽（GSH）被认为可保护结构蛋白和酶中的硫醇，以实现正常的生物学功能。晶状体具有GSH的生物合成和再生系统，以维持其大量储备。然而，老化的晶状体或处于氧化应激状态的晶状体显示GSH储备量大幅减少，一些蛋白质硫醇被氧化的非蛋白质硫醇S-硫醇化，形成蛋白质-硫醇混合二硫键，即蛋白质-S-S-谷胱甘肽（PSSG）或蛋白质-S-S-半胱氨酸（PSSC）或蛋白质-S-S-γ-谷氨酰半胱氨酸。在H₂O₂诱导的白内障模型中表明，PSSG的形成先于白内障形成前的一系列事件，始于蛋白质二硫键交联、蛋白质溶解度丧失和高分子量聚集。此外，如果及时去除氧化剂，蛋白质硫醇中的这种早期氧化损伤在H₂O₂预处理的晶状体中可自发逆转。这种脱硫醇过程似乎是通过一种氧化还原调节酶硫醇转移酶（TTase）介导的，该酶普遍存在于微生物、植物和动物组织中，包括晶状体。这种依赖GSH的低分子量（11.8 kDa）胞质酶在氧化防御中起重要作用，并可调节糖酵解途径中的关键代谢酶。该酶通过其具有邻位半胱氨酸部分的独特催化位点修复氧化损伤的蛋白质/酶，该位点可特异性地使蛋白质-S-S-谷胱甘肽脱硫醇，并恢复蛋白质游离的SH基团以实现适当的酶促或蛋白质功能。最重要的是，已证明在氧化应激条件下，当GSH过氧化物酶和GSH还原酶的其他氧化防御系统严重失活时，硫醇转移酶在培养的人及兔晶状体上皮细胞中对氧化（H₂O₂）具有显著抗性。第二种修复酶硫氧还蛋白（TRx）依赖NADPH，广泛存在于许多低等和高等生命形式中。它可以使蛋白质二硫键脱硫醇，因此是细胞中氧化还原稳态的极其重要的调节因子。最近在晶状体中发现了硫氧还蛋白，并已证明它参与氧化损伤的晶状体蛋白质/酶的修复过程。这两种酶可能协同作用，调节和修复晶状体蛋白质和酶中的硫醇，保持平衡的氧化还原电位以维持晶状体的功能。
