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Protein-bound kynurenine is a photosensitizer of oxidative damage
- Source :
-
Free Radical Biology & Medicine . Nov2004, Vol. 37 Issue 9, p1479-1489. 11p. - Publication Year :
- 2004
-
Abstract
- 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 (λ > 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. [Copyright &y& Elsevier]
- Subjects :
- *KYNURENINE
*PHOTOSENSITIZERS
*OXIDATIVE stress
*PROTEINS
Subjects
Details
- Language :
- English
- ISSN :
- 08915849
- Volume :
- 37
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Free Radical Biology & Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 14541324
- Full Text :
- https://doi.org/10.1016/j.freeradbiomed.2004.07.015