Protein-bound kynurenine is a photosensitizer of oxidative damage
Research output: Contribution to journal › Journal article › Research › peer-review
Human lens proteins become progressively modified by tryptophan-derived UV filter compounds in an age-dependent manner. One of these compounds, kynurenine, undergoes deamination at physiological pH, and the product binds covalently to nucleophilic residues in proteins via a Michael addition. Here we demonstrate that after covalent attachment of kynurenine, lens proteins become susceptible to photo-oxidation by wavelengths of light that penetrate the cornea. H2O2 and protein-bound peroxides were found to accumulate in a time-dependent manner after exposure to UV light (lambda > 305-385 nm), with shorter-wavelength light giving more peroxides. Peroxide formation was accompanied by increases in the levels of the protein-bound tyrosine oxidation products dityrosine and 3,4-dihydroxyphenylalanine, species known to be elevated in human cataract lens proteins. Experiments using D2O, which enhances the lifetime of singlet oxygen, and azide, a potent scavenger of this species, are consistent with oxidation being mediated by singlet oxygen. These findings provide a mechanistic explanation for UV light-mediated protein oxidation in cataract lenses, and also rationalize the occurrence of age-related cataract in the nuclear region of the lens, as modification of lens proteins by UV filters occurs primarily in this region.
|Journal||Free Radical Biology & Medicine|
|Number of pages||11|
|Publication status||Published - 1 Nov 2004|
- Animals, Cattle, Chromatography, High Pressure Liquid, Crystallins, Hydrolysis, Kinetics, Kynurenine, Lens, Crystalline, Nitrogen, Oxygen, Peptide Fragments, Photolysis, Photosensitizing Agents, Protein Binding, Ultraviolet Rays