Tryptophan-derived ultraviolet filter compounds covalently bound to lens proteins are photosensitizers of oxidative damage.
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-beta-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.
Mizdrak
Jasminka
J
Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW 2109, Australia.
Hains
Peter G
PG
Truscott
Roger J W
RJ
Jamie
Joanne F
JF
Davies
Michael J
MJ
D000375:Aging / Q000502:physiology / Q000528:radiation effects*; D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003459:Crystallins / Q000378:metabolism* / Q000528:radiation effects; D004591:Electrophoresis, Polyacrylamide Gel; D006861:Hydrogen Peroxide / Q000032:analysis / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism / Q000528:radiation effects*; D018384:Oxidative Stress / Q000502:physiology / Q000528:radiation effects; D014364:Tryptophan / Q000031:analogs & derivatives / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D003459:Crystallins; D014364:Tryptophan; D006861:Hydrogen Peroxide