The Hydroxyl Radical in Lens Nuclear Cataractogenesis

作者: Shanlin Fu , Roger Dean , Michael Southan , Roger Truscott

DOI: 10.1074/JBC.273.44.28603

关键词: Protein oxidationCrystallinLens proteinHydroxylationChemistryRadicalHypochloriteAmino acidHydroxyl radicalBiochemistry

摘要: Abstract Cataract is the major cause of blindness; most common form age-related, or senile, cataract. The reasons for development cataract are unknown. Here we demonstrate that nuclear associated with extensive hydroxylation protein-bound amino acid residues, which increases by up to 15-fold in case DOPA. relative abundance oxidized acids lens protein (assessed per parent acid) DOPA > o- andm-tyrosine 3-hydroxyvaline, 5-hydroxyleucine dityrosine. Nigrescent cataracts, normally transparent becomes black and opaque, contain highest level hydroxylated yet observed a biological tissue: example, 1000 DOPA, 15; 0.3; compared dityrosine, 0.05. products include representatives hydroperoxide pathways oxidation, can give rise secondary reactive species, radical otherwise. corresponds closely hydroxyl metal-dependent oxidation isolated proteins, not patterns resulting from hypochlorite tyrosyl-radical oxidation. Although very little light 300–400-nm range passes cornea filter compounds eye, nevertheless also photoxidation proteins 310 nm, part spectrum aromatic residues have residual absorbance, does aliphatic acids. Thus post-translational modification crystallins radicals/Fenton systems seems dominate their vivo it could explain known features such cataractogenesis.

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