Protein-bound kynurenine is a photosensitizer of oxidative damage

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

Research output: Contribution to journalArticleResearchpeer-review

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. H 2O 2 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 D 2O, 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.

LanguageEnglish
Pages1479-1489
Number of pages11
JournalFree Radical Biology and Medicine
Volume37
Issue number9
DOIs
Publication statusPublished - 1 Nov 2004
Externally publishedYes

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Kynurenine
Crystallins
Photosensitizing Agents
Peroxides
Singlet Oxygen
Ultraviolet Rays
Ultraviolet radiation
Oxidation
Cataract
Lenses
Proteins
Light
Wavelength
Dihydroxyphenylalanine
Deamination
Photooxidation
Azides
Tryptophan
Cornea
Tyrosine

Cite this

Parker, Nicole R. ; Jamie, Joanne F. ; Davies, Michael J. ; Truscott, Roger J W. / Protein-bound kynurenine is a photosensitizer of oxidative damage. In: Free Radical Biology and Medicine. 2004 ; Vol. 37, No. 9. pp. 1479-1489.
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Protein-bound kynurenine is a photosensitizer of oxidative damage. / Parker, Nicole R.; Jamie, Joanne F.; Davies, Michael J.; Truscott, Roger J W.

In: Free Radical Biology and Medicine, Vol. 37, No. 9, 01.11.2004, p. 1479-1489.

Research output: Contribution to journalArticleResearchpeer-review

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