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.
| Language | English |
|---|---|
| Pages | 1479-1489 |
| Number of pages | 11 |
| Journal | Free Radical Biology and Medicine |
| Volume | 37 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 1 Nov 2004 |
| Externally published | Yes |
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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 journal › Article › Research › peer-review
TY - JOUR
T1 - Protein-bound kynurenine is a photosensitizer of oxidative damage
AU - Parker, Nicole R.
AU - Jamie, Joanne F.
AU - Davies, Michael J.
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. 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.
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. 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.
UR - http://www.scopus.com/inward/record.url?scp=5344236032&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2004.07.015
DO - 10.1016/j.freeradbiomed.2004.07.015
M3 - Article
VL - 37
SP - 1479
EP - 1489
JO - Free Radical Biology and Medicine
T2 - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 9
ER -