The hydroxyl radical in lens nuclear cataractogenesis
The hydroxyl radical in lens nuclear cataractogenesis
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DOI：
10.1074/jbc.273.44.28603
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发表时间：
1998-10-30
影响因子：
4.8
通讯作者：
Truscott, R
中科院分区：
文献类型：
--
作者：
Fu, SL;Dean, R;Truscott, R
白内障是失明的主要原因；最常见的形式是与年龄相关的，或老年性白内障，白内障发展的原因尚不清楚，在这里，我们证明核性白内障与蛋白质结合的氨基酸残基的广泛羟基化有关，在DOPA的情况下，随着白内障的发展，羟基化程度增加了15倍。晶状体蛋白中氧化氨基酸的相对丰度（按亲本氨基酸评估）是DOPA > 0 -和m-酪氨酸> 3-羟缬氨酸。通常透明的晶状体变成黑色和不透明的黑性白内障，在生物组织中含有最高水平的羟基化氨基酸：例如，每1000个亲本氨基酸残基中，多巴为15；3-hydroxyvaline 0.3;与二酪氨酸相比，0.05，产物包括氢过氧化物和多巴蛋白氧化途径的代表，可以产生二次反应物质，自由基等。观察到的相对丰度与羟基自由基或分离蛋白的金属依赖氧化产物的丰度密切相关，而与次氯酸盐或酪氨酸自由基氧化产生的模式无关。尽管在300-400纳米范围内很少有光通过角膜和眼睛的过滤化合物，但我们也证明了晶状体蛋白在310纳米的光氧化作用下，光谱中蛋白质芳香残基有残余吸光度的部分，不会产生羟基化的脂肪族氨基酸。因此，羟基自由基/芬顿系统对晶体蛋白的翻译后修饰似乎主导了它们的体内氧化，这可以解释这种核白内障发生的已知特征。
Cataract is the major cause of blindness; the most common form is age-related, or senile, cataract, The reasons for the development of cataract are unknown, Here we demonstrate that nuclear cataract is associated with the extensive hydroxylation of protein-bound amino acid residues, which increases with the development of cataract by up to 15-foId in the case of DOPA, The relative abundance of the oxidized amino acids in lens protein (assessed per parent amino acid) is DOPA > o- and m-tyrosine > 3-hydroxyvaline, 5-hydroxyleucine > dityrosine, Nigrescent cataracts, in which the normally transparent lens becomes black and opaque, contain the highest level of hydroxylated amino acids yet observed in a biological tissue: for example, per 1000 parent amino acid residues, DOPA, 15; 3-hydroxyvaline, 0.3; compared with dityrosine, 0.05, The products include representatives of the hydroperoxide and DOPA pathways of protein oxidation, which can give rise to secondary reactive species, radical and otherwise. The observed relative abundance corresponds closely with that of products of hydroxyl radical or metal-dependent oxidation of isolated proteins, and not with the patterns resulting from hypochlorite or tyrosyl-radical oxidation, Although very Little light in the 300-400-nm range passes the cornea and the filter compounds of the eye, we nevertheless also demonstrate that photoxidation of lens proteins with light of 310 nm, the part of the spectrum in which protein aromatic residues have residual absorbance, does not give rise to the hydroxylated aliphatic amino acids. Thus the post-translational modification of crystallins by hydroxyl radicals/Fenton systems seems to dominate their in vivo oxidation, and it could explain the known features of such nuclear cataractogenesis.