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

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

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 Jonathan.

In: Free Radical Biology & Medicine, Vol. 44, No. 6, 15.03.2008, p. 1108-19.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Mizdrak, J, Hains, PG, Truscott, RJW, Jamie, JF & Davies, MJ 2008, 'Tryptophan-derived ultraviolet filter compounds covalently bound to lens proteins are photosensitizers of oxidative damage', Free Radical Biology & Medicine, vol. 44, no. 6, pp. 1108-19. https://doi.org/10.1016/j.freeradbiomed.2007.12.003

APA

Mizdrak, J., Hains, P. G., Truscott, R. J. W., Jamie, J. F., & Davies, M. J. (2008). Tryptophan-derived ultraviolet filter compounds covalently bound to lens proteins are photosensitizers of oxidative damage. Free Radical Biology & Medicine, 44(6), 1108-19. https://doi.org/10.1016/j.freeradbiomed.2007.12.003

Vancouver

Mizdrak J, Hains PG, Truscott RJW, Jamie JF, Davies MJ. Tryptophan-derived ultraviolet filter compounds covalently bound to lens proteins are photosensitizers of oxidative damage. Free Radical Biology & Medicine. 2008 Mar 15;44(6):1108-19. https://doi.org/10.1016/j.freeradbiomed.2007.12.003

Author

Mizdrak, Jasminka ; Hains, Peter G ; Truscott, Roger J W ; Jamie, Joanne F ; Davies, Michael Jonathan. / Tryptophan-derived ultraviolet filter compounds covalently bound to lens proteins are photosensitizers of oxidative damage. In: Free Radical Biology & Medicine. 2008 ; Vol. 44, No. 6. pp. 1108-19.

Bibtex

@article{339fa5c8e15445ab86d526f38f961b53,
title = "Tryptophan-derived ultraviolet filter compounds covalently bound to lens proteins are photosensitizers of oxidative damage",
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-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.",
keywords = "Aging, Animals, Cattle, Chromatography, High Pressure Liquid, Crystallins, Electrophoresis, Polyacrylamide Gel, Hydrogen Peroxide, Lens, Crystalline, Oxidative Stress, Tryptophan, Ultraviolet Rays",
author = "Jasminka Mizdrak and Hains, {Peter G} and Truscott, {Roger J W} and Jamie, {Joanne F} and Davies, {Michael Jonathan}",
year = "2008",
month = "3",
day = "15",
doi = "10.1016/j.freeradbiomed.2007.12.003",
language = "English",
volume = "44",
pages = "1108--19",
journal = "Free Radical Biology & Medicine",
issn = "0891-5849",
publisher = "Elsevier",
number = "6",

}

RIS

TY - JOUR

T1 - Tryptophan-derived ultraviolet filter compounds covalently bound to lens proteins are photosensitizers of oxidative damage

AU - Mizdrak, Jasminka

AU - Hains, Peter G

AU - Truscott, Roger J W

AU - Jamie, Joanne F

AU - Davies, Michael Jonathan

PY - 2008/3/15

Y1 - 2008/3/15

N2 - 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.

AB - 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.

KW - Aging

KW - Animals

KW - Cattle

KW - Chromatography, High Pressure Liquid

KW - Crystallins

KW - Electrophoresis, Polyacrylamide Gel

KW - Hydrogen Peroxide

KW - Lens, Crystalline

KW - Oxidative Stress

KW - Tryptophan

KW - Ultraviolet Rays

U2 - 10.1016/j.freeradbiomed.2007.12.003

DO - 10.1016/j.freeradbiomed.2007.12.003

M3 - Journal article

C2 - 18206985

VL - 44

SP - 1108

EP - 1119

JO - Free Radical Biology & Medicine

JF - Free Radical Biology & Medicine

SN - 0891-5849

IS - 6

ER -

ID: 129670887