Garland D
Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
Exp Eye Res. 1990 Jun;50(6):677-82. doi: 10.1016/0014-4835(90)90113-9.
The evidence reviewed here supports the hypothesis that metal catalyzed oxidation reactions occur in the lens and may make a significant contribution to the changes seen in the lens with age and in cataract formation. The major support for this hypothesis is as follows. (1) All of the components of the non-enzymic metal catalyzed oxidation systems are present in the lens normally. Ascorbate, glutathione and oxygen are present in much lower concentrations. Although, even at low concentrations, the reactions could occur over many years with significant consequences. Components of some of the enzymic systems are also present, although primarily in the epithelial layer and outer cortical region. Copper and iron levels may be increased in some cataracts. (2) Protein carbonyl derivatives are increased in both aging and cataractous lenses. Amino acid-derived protein carbonyl derivatives have only been demonstrated in oxidative reactions derived from oxygen radical generation, particularly those catalyzed by metal-catalyzed oxidation systems. (3) Treatment of isolated bovine crystallins with metal catalyzed oxidation systems generates modifications similar to those found in vivo. The proposed mechanism of site-specific metal catalyzed oxidation appears to be a feasible mechanism of oxidation in the lens, and verification of the mechanism requires further study. Although the focus of this manuscript has been on the oxidative modification induced in proteins,m oxidative damage to DNA or membrane resulting from similar mechanisms may also play an important role in alteration of lens function during aging and cataractogenesis.
本文所综述的证据支持这样一种假说，即金属催化的氧化反应发生在晶状体中，并且可能对晶状体随年龄增长以及白内障形成过程中所出现的变化起到重要作用。对这一假说的主要支持如下：（1）非酶促金属催化氧化系统的所有成分在晶状体中均正常存在。抗坏血酸、谷胱甘肽和氧气的浓度要低得多。尽管即使浓度很低，这些反应也可能在多年间发生并产生重大影响。一些酶促系统的成分也存在，不过主要存在于上皮层和皮质外层区域。在某些白内障中，铜和铁的含量可能会增加。（2）在老化和白内障晶状体中，蛋白质羰基衍生物均有所增加。氨基酸衍生的蛋白质羰基衍生物仅在由氧自由基产生引发的氧化反应中被证实，尤其是那些由金属催化氧化系统催化的反应。（3）用金属催化氧化系统处理分离出的牛晶状体蛋白会产生与体内发现的修饰类似的结果。所提出的位点特异性金属催化氧化机制似乎是晶状体中一种可行的氧化机制，对该机制的验证还需要进一步研究。尽管本文的重点一直是蛋白质中诱导的氧化修饰，但由类似机制导致的对DNA或膜的氧化损伤在衰老和白内障形成过程中晶状体功能改变方面可能也起着重要作用。
