Protein-bound kynurenine is a photosensitizer of oxidative damage

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Protein-bound kynurenine is a photosensitizer of oxidative damage. / Parker, Nicole R; Jamie, Joanne F; Davies, Michael Jonathan; Truscott, Roger J W.

In: Free Radical Biology & Medicine, Vol. 37, No. 9, 01.11.2004, p. 1479-89.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Parker, NR, Jamie, JF, Davies, MJ & Truscott, RJW 2004, 'Protein-bound kynurenine is a photosensitizer of oxidative damage', Free Radical Biology & Medicine, vol. 37, no. 9, pp. 1479-89. https://doi.org/10.1016/j.freeradbiomed.2004.07.015

APA

Parker, N. R., Jamie, J. F., Davies, M. J., & Truscott, R. J. W. (2004). Protein-bound kynurenine is a photosensitizer of oxidative damage. Free Radical Biology & Medicine, 37(9), 1479-89. https://doi.org/10.1016/j.freeradbiomed.2004.07.015

Vancouver

Parker NR, Jamie JF, Davies MJ, Truscott RJW. Protein-bound kynurenine is a photosensitizer of oxidative damage. Free Radical Biology & Medicine. 2004 Nov 1;37(9):1479-89. https://doi.org/10.1016/j.freeradbiomed.2004.07.015

Author

Parker, Nicole R ; Jamie, Joanne F ; Davies, Michael Jonathan ; Truscott, Roger J W. / Protein-bound kynurenine is a photosensitizer of oxidative damage. In: Free Radical Biology & Medicine. 2004 ; Vol. 37, No. 9. pp. 1479-89.

Bibtex

@article{87e0c7cb95574e3d8e4a313a41996a93,
title = "Protein-bound kynurenine is a photosensitizer of oxidative damage",
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.",
keywords = "Animals, Cattle, Chromatography, High Pressure Liquid, Crystallins, Hydrolysis, Kinetics, Kynurenine, Lens, Crystalline, Nitrogen, Oxygen, Peptide Fragments, Photolysis, Photosensitizing Agents, Protein Binding, Ultraviolet Rays",
author = "Parker, {Nicole R} and Jamie, {Joanne F} and Davies, {Michael Jonathan} and Truscott, {Roger J W}",
year = "2004",
month = "11",
day = "1",
doi = "10.1016/j.freeradbiomed.2004.07.015",
language = "English",
volume = "37",
pages = "1479--89",
journal = "Free Radical Biology & Medicine",
issn = "0891-5849",
publisher = "Elsevier",
number = "9",

}

RIS

TY - JOUR

T1 - Protein-bound kynurenine is a photosensitizer of oxidative damage

AU - Parker, Nicole R

AU - Jamie, Joanne F

AU - Davies, Michael Jonathan

AU - Truscott, Roger J W

PY - 2004/11/1

Y1 - 2004/11/1

N2 - 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.

AB - 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.

KW - Animals

KW - Cattle

KW - Chromatography, High Pressure Liquid

KW - Crystallins

KW - Hydrolysis

KW - Kinetics

KW - Kynurenine

KW - Lens, Crystalline

KW - Nitrogen

KW - Oxygen

KW - Peptide Fragments

KW - Photolysis

KW - Photosensitizing Agents

KW - Protein Binding

KW - Ultraviolet Rays

U2 - 10.1016/j.freeradbiomed.2004.07.015

DO - 10.1016/j.freeradbiomed.2004.07.015

M3 - Journal article

VL - 37

SP - 1479

EP - 1489

JO - Free Radical Biology & Medicine

JF - Free Radical Biology & Medicine

SN - 0891-5849

IS - 9

ER -

ID: 129672113