Paik D C, Dillon J
Department of Ophthalmology, Harkness Eye Institute, Columbia Presbyterian Medical Center, New York, New York, USA.
Exp Eye Res. 2000 Jan;70(1):73-80. doi: 10.1006/exer.1999.0761.
Recent work has explored the potential deleterious role that nitric oxide (NO) and its derivatives may have in human disease. The many by-products of NO include nitrite ion, which accumulates in the anterior chamber during ocular inflammation and can be derived from cigarette smoking. Cigarette smoking has been strongly linked to nuclear cataract formation, although the mechanism remains unknown. We have previously observed that nitrite reactions with the matrix proteins elastin and collagen produce damaging effects that mimic those observed in age- and smoking-related illnesses. In the present study we report on the reaction of nitrite with alpha crystallin, the major lens matrix protein. Incubations at neutral pH and body temperature of nitrite with alpha crystallin resulted in protein modifications indicative of oxidative damage and similar to changes seen in the aging lens as well as cataracts. These include increased fluorescence, yellowing and protein cross-linking. L-kynurenine, a tryptophan derivative, was identified as a reaction product. L-kynurenine was also formed from the reaction of nitrite with free tryptophan. Thus, this non-enzymatic nitration of alpha crystallin provides a novel mechanism by which lens proteins may be damaged in vivo. Since human exposure to nitrite is increased by cigarette smoking, this reaction could provide an explanation for the association between nuclear cataracts and smoking.
近期的研究探讨了一氧化氮（NO）及其衍生物在人类疾病中可能具有的潜在有害作用。NO的许多副产物包括亚硝酸根离子，其在眼部炎症期间会在前房积聚，并且可能来源于吸烟。吸烟与核性白内障的形成密切相关，尽管其机制尚不清楚。我们之前观察到，亚硝酸与基质蛋白弹性蛋白和胶原蛋白的反应会产生破坏性影响，类似于在与年龄和吸烟相关的疾病中观察到的影响。在本研究中，我们报告了亚硝酸与晶状体主要基质蛋白α-晶体蛋白的反应。在中性pH值和体温下，将亚硝酸与α-晶体蛋白一起孵育，会导致蛋白质发生修饰，表明存在氧化损伤，且类似于在老化晶状体以及白内障中看到的变化。这些变化包括荧光增强、变黄和蛋白质交联。L-犬尿氨酸，一种色氨酸衍生物，被鉴定为反应产物。L-犬尿氨酸也由亚硝酸与游离色氨酸的反应形成。因此，α-晶体蛋白的这种非酶促硝化作用提供了一种新的机制，通过该机制晶状体蛋白可能在体内受到损伤。由于吸烟会增加人体对亚硝酸的接触，这种反应可以解释核性白内障与吸烟之间的关联。
