Protein-bound kynurenine is a photosensitizer of oxidative damage

Nicole R Parker, Joanne F Jamie, Michael Jonathan Davies, Roger J W Truscott

Research output: Contribution to journalJournal articleResearchpeer-review

95 Citations (Scopus)

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 (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.

Original languageEnglish
JournalFree Radical Biology & Medicine
Volume37
Issue number9
Pages (from-to)1479-89
Number of pages11
ISSN0891-5849
DOIs
Publication statusPublished - 1 Nov 2004
Externally publishedYes

Keywords

  • Animals
  • Cattle
  • Chromatography, High Pressure Liquid
  • Crystallins
  • Hydrolysis
  • Kinetics
  • Kynurenine
  • Lens, Crystalline
  • Nitrogen
  • Oxygen
  • Peptide Fragments
  • Photolysis
  • Photosensitizing Agents
  • Protein Binding
  • Ultraviolet Rays

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