Tryptophan-derived ultraviolet filter compounds covalently bound to lens proteins are photosensitizers of oxidative damage

Jasminka Mizdrak, Peter G. Hains, Roger J W Truscott, Joanne F. Jamie, Michael J. Davies

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The human eye is chronically exposed to light of wavelengths > 300 nm. In the young human lens, light of wavelength 300-400 nm is predominantly absorbed by the free Trp derivatives kynurenine (Kyn), 3-hydroxykynurenine (3OHKyn), and 3-hydroxykynurenine-O-β-D-glucoside (3OHKynG). These ultraviolet (UV) filter compounds are poor photosensitizers. With age, the levels of the free UV filters in the lens decreases and those of protein-bound UV filters increases. The photochemical behavior of these protein-bound UV filters and their role in UV damage are poorly elucidated and are examined here. UVA illumination of protein-bound UV filters generated peroxides (principally H2O2) in a metabolite-, photolysis-time-, and wavelength-dependent manner. Unmodified proteins, free Trp metabolites, and Trp metabolites that do not bind to lens proteins gave low peroxide yields. Protein-bound 3OHKyn (principally at Cys residues) yielded more peroxide than comparable Kyn and 3OHKynG adducts. Studies using D2O and sodium azide implicated 1O2 as a key intermediate. Illumination of the protein-bound adducts also yielded protein-bound Tyr oxidation products (DOPA, di-tyrosine) and protein cross-links via alternative mechanisms. These data indicate that the covalent modification of lens proteins by Kyn derivatives yields photosensitizers that may enhance oxidation in older lenses and contribute to age-related nuclear cataract.

LanguageEnglish
Pages1108-1119
Number of pages12
JournalFree Radical Biology and Medicine
Volume44
Issue number6
DOIs
Publication statusPublished - 15 Mar 2008

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Crystallins
Photosensitizing Agents
Tryptophan
Kynurenine
Peroxides
Proteins
Lenses
Metabolites
Glucosides
Lighting
Wavelength
Light
Sodium Azide
Derivatives
Photolysis
Oxidation
Tyrosine
3-hydroxykynurenine

Cite this

Mizdrak, Jasminka ; Hains, Peter G. ; Truscott, Roger J W ; Jamie, Joanne F. ; Davies, Michael J. / Tryptophan-derived ultraviolet filter compounds covalently bound to lens proteins are photosensitizers of oxidative damage. In: Free Radical Biology and Medicine. 2008 ; Vol. 44, No. 6. pp. 1108-1119.
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abstract = "The human eye is chronically exposed to light of wavelengths > 300 nm. In the young human lens, light of wavelength 300-400 nm is predominantly absorbed by the free Trp derivatives kynurenine (Kyn), 3-hydroxykynurenine (3OHKyn), and 3-hydroxykynurenine-O-β-D-glucoside (3OHKynG). These ultraviolet (UV) filter compounds are poor photosensitizers. With age, the levels of the free UV filters in the lens decreases and those of protein-bound UV filters increases. The photochemical behavior of these protein-bound UV filters and their role in UV damage are poorly elucidated and are examined here. UVA illumination of protein-bound UV filters generated peroxides (principally H2O2) in a metabolite-, photolysis-time-, and wavelength-dependent manner. Unmodified proteins, free Trp metabolites, and Trp metabolites that do not bind to lens proteins gave low peroxide yields. Protein-bound 3OHKyn (principally at Cys residues) yielded more peroxide than comparable Kyn and 3OHKynG adducts. Studies using D2O and sodium azide implicated 1O2 as a key intermediate. Illumination of the protein-bound adducts also yielded protein-bound Tyr oxidation products (DOPA, di-tyrosine) and protein cross-links via alternative mechanisms. These data indicate that the covalent modification of lens proteins by Kyn derivatives yields photosensitizers that may enhance oxidation in older lenses and contribute to age-related nuclear cataract.",
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Tryptophan-derived ultraviolet filter compounds covalently bound to lens proteins are photosensitizers of oxidative damage. / Mizdrak, Jasminka; Hains, Peter G.; Truscott, Roger J W; Jamie, Joanne F.; Davies, Michael J.

In: Free Radical Biology and Medicine, Vol. 44, No. 6, 15.03.2008, p. 1108-1119.

Research output: Contribution to journalArticleResearchpeer-review

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