Cross-linking of lens crystallin proteins induced by tryptophan metabolites and metal ions: implications for cataract development

Research output: Contribution to journalJournal articleResearchpeer-review

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Cross-linking of lens crystallin proteins induced by tryptophan metabolites and metal ions : implications for cataract development. / Tweeddale, Helen J; Hawkins, Clare Louise; Janmie, Joane F; Truscott, Roger J W; Davies, Michael J.

In: Free Radical Research, Vol. 50, No. 10, 10.2016, p. 1116-1130.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Tweeddale, HJ, Hawkins, CL, Janmie, JF, Truscott, RJW & Davies, MJ 2016, 'Cross-linking of lens crystallin proteins induced by tryptophan metabolites and metal ions: implications for cataract development', Free Radical Research, vol. 50, no. 10, pp. 1116-1130. https://doi.org/10.1080/10715762.2016.1210802

APA

Tweeddale, H. J., Hawkins, C. L., Janmie, J. F., Truscott, R. J. W., & Davies, M. J. (2016). Cross-linking of lens crystallin proteins induced by tryptophan metabolites and metal ions: implications for cataract development. Free Radical Research, 50(10), 1116-1130. https://doi.org/10.1080/10715762.2016.1210802

Vancouver

Tweeddale HJ, Hawkins CL, Janmie JF, Truscott RJW, Davies MJ. Cross-linking of lens crystallin proteins induced by tryptophan metabolites and metal ions: implications for cataract development. Free Radical Research. 2016 Oct;50(10):1116-1130. https://doi.org/10.1080/10715762.2016.1210802

Author

Tweeddale, Helen J ; Hawkins, Clare Louise ; Janmie, Joane F ; Truscott, Roger J W ; Davies, Michael J. / Cross-linking of lens crystallin proteins induced by tryptophan metabolites and metal ions : implications for cataract development. In: Free Radical Research. 2016 ; Vol. 50, No. 10. pp. 1116-1130.

Bibtex

@article{65bc81c4689d4783b5eb92942b389b58,
title = "Cross-linking of lens crystallin proteins induced by tryptophan metabolites and metal ions: implications for cataract development",
abstract = "Long-wavelength solar UV radiation is implicated in photodamage to the human eye. The human lens contains multiple tryptophan-derived compounds that have significant absorbance bands in the UVA region (λ 315-400 nm) that act as efficient physical filters for these wavelengths. The concentrations of many of these UV filter compounds decrease with increase in age, resulting in diminished protection, increased oxidative damage and the accumulation of modified proteins implicated in nuclear cataract formation. This damage may arise via the formation of α,β-unsaturated carbonyls from the UV filter compounds, adduction to lens proteins and subsequent action as photosensitizers, and/or via the reactions of redox-active transition metal ions that accumulate in aged human lenses. The latter may promote the oxidation of free, or protein-bound, o-aminophenols, such as the UV filter compounds 3-hydroxykynurenine (3OHKyn) and 3-hydroxyanthranilic acid (3OHAA). It is shown here that Cu(II), and to a lesser extent Fe(III), enhance oxidation of free 3OHKyn, 3OHAA and 3OHKyn bound to specific amino acids and lens proteins, with this resulting in increased cross-linking of lens proteins. These data indicate that elevated levels of transition metal ions in aging lenses can enhance the loss of protective UV filter compounds, and contribute to the formation of high-molecular-mass dysfunctional crystallin proteins in a light-independent manner. These reactions may contribute to the formation of lens cataracts in humans.",
author = "Tweeddale, {Helen J} and Hawkins, {Clare Louise} and Janmie, {Joane F} and Truscott, {Roger J W} and Davies, {Michael J}",
year = "2016",
month = "10",
doi = "10.1080/10715762.2016.1210802",
language = "English",
volume = "50",
pages = "1116--1130",
journal = "Free Radical Research",
issn = "1071-5762",
publisher = "Taylor & Francis",
number = "10",

}

RIS

TY - JOUR

T1 - Cross-linking of lens crystallin proteins induced by tryptophan metabolites and metal ions

T2 - implications for cataract development

AU - Tweeddale, Helen J

AU - Hawkins, Clare Louise

AU - Janmie, Joane F

AU - Truscott, Roger J W

AU - Davies, Michael J

PY - 2016/10

Y1 - 2016/10

N2 - Long-wavelength solar UV radiation is implicated in photodamage to the human eye. The human lens contains multiple tryptophan-derived compounds that have significant absorbance bands in the UVA region (λ 315-400 nm) that act as efficient physical filters for these wavelengths. The concentrations of many of these UV filter compounds decrease with increase in age, resulting in diminished protection, increased oxidative damage and the accumulation of modified proteins implicated in nuclear cataract formation. This damage may arise via the formation of α,β-unsaturated carbonyls from the UV filter compounds, adduction to lens proteins and subsequent action as photosensitizers, and/or via the reactions of redox-active transition metal ions that accumulate in aged human lenses. The latter may promote the oxidation of free, or protein-bound, o-aminophenols, such as the UV filter compounds 3-hydroxykynurenine (3OHKyn) and 3-hydroxyanthranilic acid (3OHAA). It is shown here that Cu(II), and to a lesser extent Fe(III), enhance oxidation of free 3OHKyn, 3OHAA and 3OHKyn bound to specific amino acids and lens proteins, with this resulting in increased cross-linking of lens proteins. These data indicate that elevated levels of transition metal ions in aging lenses can enhance the loss of protective UV filter compounds, and contribute to the formation of high-molecular-mass dysfunctional crystallin proteins in a light-independent manner. These reactions may contribute to the formation of lens cataracts in humans.

AB - Long-wavelength solar UV radiation is implicated in photodamage to the human eye. The human lens contains multiple tryptophan-derived compounds that have significant absorbance bands in the UVA region (λ 315-400 nm) that act as efficient physical filters for these wavelengths. The concentrations of many of these UV filter compounds decrease with increase in age, resulting in diminished protection, increased oxidative damage and the accumulation of modified proteins implicated in nuclear cataract formation. This damage may arise via the formation of α,β-unsaturated carbonyls from the UV filter compounds, adduction to lens proteins and subsequent action as photosensitizers, and/or via the reactions of redox-active transition metal ions that accumulate in aged human lenses. The latter may promote the oxidation of free, or protein-bound, o-aminophenols, such as the UV filter compounds 3-hydroxykynurenine (3OHKyn) and 3-hydroxyanthranilic acid (3OHAA). It is shown here that Cu(II), and to a lesser extent Fe(III), enhance oxidation of free 3OHKyn, 3OHAA and 3OHKyn bound to specific amino acids and lens proteins, with this resulting in increased cross-linking of lens proteins. These data indicate that elevated levels of transition metal ions in aging lenses can enhance the loss of protective UV filter compounds, and contribute to the formation of high-molecular-mass dysfunctional crystallin proteins in a light-independent manner. These reactions may contribute to the formation of lens cataracts in humans.

U2 - 10.1080/10715762.2016.1210802

DO - 10.1080/10715762.2016.1210802

M3 - Journal article

C2 - 27383194

VL - 50

SP - 1116

EP - 1130

JO - Free Radical Research

JF - Free Radical Research

SN - 1071-5762

IS - 10

ER -

ID: 173125930