Reversible binding of kynurenine to lens proteins: potential protection by glutathione in young lenses

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Reversible binding of kynurenine to lens proteins : potential protection by glutathione in young lenses. / Parker, Nicole R; Korlimbinis, Anastasia; Jamie, Joanne F; Davies, Michael Jonathan; Truscott, Roger J W.

In: Investigative Ophthalmology & Visual Science, Vol. 48, No. 8, 08.2007, p. 3705-13.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Parker, NR, Korlimbinis, A, Jamie, JF, Davies, MJ & Truscott, RJW 2007, 'Reversible binding of kynurenine to lens proteins: potential protection by glutathione in young lenses', Investigative Ophthalmology & Visual Science, vol. 48, no. 8, pp. 3705-13. https://doi.org/10.1167/iovs.06-1061

APA

Parker, N. R., Korlimbinis, A., Jamie, J. F., Davies, M. J., & Truscott, R. J. W. (2007). Reversible binding of kynurenine to lens proteins: potential protection by glutathione in young lenses. Investigative Ophthalmology & Visual Science, 48(8), 3705-13. https://doi.org/10.1167/iovs.06-1061

Vancouver

Parker NR, Korlimbinis A, Jamie JF, Davies MJ, Truscott RJW. Reversible binding of kynurenine to lens proteins: potential protection by glutathione in young lenses. Investigative Ophthalmology & Visual Science. 2007 Aug;48(8):3705-13. https://doi.org/10.1167/iovs.06-1061

Author

Parker, Nicole R ; Korlimbinis, Anastasia ; Jamie, Joanne F ; Davies, Michael Jonathan ; Truscott, Roger J W. / Reversible binding of kynurenine to lens proteins : potential protection by glutathione in young lenses. In: Investigative Ophthalmology & Visual Science. 2007 ; Vol. 48, No. 8. pp. 3705-13.

Bibtex

@article{58bb8c903d6d414caed143ae2fb9467a,
title = "Reversible binding of kynurenine to lens proteins: potential protection by glutathione in young lenses",
abstract = "PURPOSE: Human ultraviolet light (UV) filters, such as kynurenine (Kyn), readily deaminate to reactive unsaturated ketones that covalently modify proteins in older human lenses. The aim of this study was to examine in vitro rates of formation and decomposition of the three major Kyn-amino acid adducts and possible consequences for the lens.METHODS: The t-Boc-protected Kyn-His, Kyn-Lys, and Kyn-Cys adducts and Kyn-Cys were synthesized from the corresponding amino acids and Kyn. Calf lens proteins were modified with Kyn by incubation at pH 7. Stability and competition studies of the adducts were conducted under physiological conditions. Kyn-amino acids and their decomposition products were quantified using HPLC.RESULTS: At physiological pH, Kyn-Cys adducts formed more rapidly than either Lys or His adducts, but they also decomposed readily. By contrast, His adducts were stable. Cysteine (Cys) residues in beta-crystallins were major sites of modification. The Kyn moiety, initially bound to Cys residues, was found to transfer to other amino acids. Glutathione promoted the breakdown of Kyn-Cys.CONCLUSIONS: These data may help explain why proteins in young lenses are not modified by UV filters in situ. The initial phase of the modification of proteins in the human lens by UV filters may be a dynamic process. In lenses, Cys residues of crystallins modify preferentially, but these adducts also decompose to release deaminated Kyn. This can then potentially react with other amino acids. Glutathione, which is present in high concentrations in the lenses of young people, may play a vital role in keeping proteins free from modification by intercepting reactive deaminated kynurenines formed by the spontaneous breakdown of free UV filters, promoting the decomposition of Kyn-Cys residues, and sequestering the unsaturated ketones once they are released from modified proteins.",
keywords = "Aging, Animals, Binding, Competitive, Cattle, Crystallins, Cysteine, Glutathione, Histidine, Hydrogen-Ion Concentration, In Vitro Techniques, Ketones, Kynurenine, Lens, Crystalline, Protein Processing, Post-Translational, Ultraviolet Rays",
author = "Parker, {Nicole R} and Anastasia Korlimbinis and Jamie, {Joanne F} and Davies, {Michael Jonathan} and Truscott, {Roger J W}",
year = "2007",
month = "8",
doi = "10.1167/iovs.06-1061",
language = "English",
volume = "48",
pages = "3705--13",
journal = "Investigative Ophthalmology & Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology",
number = "8",

}

RIS

TY - JOUR

T1 - Reversible binding of kynurenine to lens proteins

T2 - potential protection by glutathione in young lenses

AU - Parker, Nicole R

AU - Korlimbinis, Anastasia

AU - Jamie, Joanne F

AU - Davies, Michael Jonathan

AU - Truscott, Roger J W

PY - 2007/8

Y1 - 2007/8

N2 - PURPOSE: Human ultraviolet light (UV) filters, such as kynurenine (Kyn), readily deaminate to reactive unsaturated ketones that covalently modify proteins in older human lenses. The aim of this study was to examine in vitro rates of formation and decomposition of the three major Kyn-amino acid adducts and possible consequences for the lens.METHODS: The t-Boc-protected Kyn-His, Kyn-Lys, and Kyn-Cys adducts and Kyn-Cys were synthesized from the corresponding amino acids and Kyn. Calf lens proteins were modified with Kyn by incubation at pH 7. Stability and competition studies of the adducts were conducted under physiological conditions. Kyn-amino acids and their decomposition products were quantified using HPLC.RESULTS: At physiological pH, Kyn-Cys adducts formed more rapidly than either Lys or His adducts, but they also decomposed readily. By contrast, His adducts were stable. Cysteine (Cys) residues in beta-crystallins were major sites of modification. The Kyn moiety, initially bound to Cys residues, was found to transfer to other amino acids. Glutathione promoted the breakdown of Kyn-Cys.CONCLUSIONS: These data may help explain why proteins in young lenses are not modified by UV filters in situ. The initial phase of the modification of proteins in the human lens by UV filters may be a dynamic process. In lenses, Cys residues of crystallins modify preferentially, but these adducts also decompose to release deaminated Kyn. This can then potentially react with other amino acids. Glutathione, which is present in high concentrations in the lenses of young people, may play a vital role in keeping proteins free from modification by intercepting reactive deaminated kynurenines formed by the spontaneous breakdown of free UV filters, promoting the decomposition of Kyn-Cys residues, and sequestering the unsaturated ketones once they are released from modified proteins.

AB - PURPOSE: Human ultraviolet light (UV) filters, such as kynurenine (Kyn), readily deaminate to reactive unsaturated ketones that covalently modify proteins in older human lenses. The aim of this study was to examine in vitro rates of formation and decomposition of the three major Kyn-amino acid adducts and possible consequences for the lens.METHODS: The t-Boc-protected Kyn-His, Kyn-Lys, and Kyn-Cys adducts and Kyn-Cys were synthesized from the corresponding amino acids and Kyn. Calf lens proteins were modified with Kyn by incubation at pH 7. Stability and competition studies of the adducts were conducted under physiological conditions. Kyn-amino acids and their decomposition products were quantified using HPLC.RESULTS: At physiological pH, Kyn-Cys adducts formed more rapidly than either Lys or His adducts, but they also decomposed readily. By contrast, His adducts were stable. Cysteine (Cys) residues in beta-crystallins were major sites of modification. The Kyn moiety, initially bound to Cys residues, was found to transfer to other amino acids. Glutathione promoted the breakdown of Kyn-Cys.CONCLUSIONS: These data may help explain why proteins in young lenses are not modified by UV filters in situ. The initial phase of the modification of proteins in the human lens by UV filters may be a dynamic process. In lenses, Cys residues of crystallins modify preferentially, but these adducts also decompose to release deaminated Kyn. This can then potentially react with other amino acids. Glutathione, which is present in high concentrations in the lenses of young people, may play a vital role in keeping proteins free from modification by intercepting reactive deaminated kynurenines formed by the spontaneous breakdown of free UV filters, promoting the decomposition of Kyn-Cys residues, and sequestering the unsaturated ketones once they are released from modified proteins.

KW - Aging

KW - Animals

KW - Binding, Competitive

KW - Cattle

KW - Crystallins

KW - Cysteine

KW - Glutathione

KW - Histidine

KW - Hydrogen-Ion Concentration

KW - In Vitro Techniques

KW - Ketones

KW - Kynurenine

KW - Lens, Crystalline

KW - Protein Processing, Post-Translational

KW - Ultraviolet Rays

U2 - 10.1167/iovs.06-1061

DO - 10.1167/iovs.06-1061

M3 - Journal article

C2 - 17652742

VL - 48

SP - 3705

EP - 3713

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

SN - 0146-0404

IS - 8

ER -

ID: 129671189