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

Helen J. Tweeddale, Clare L. Hawkins, Joane F. Janmie, Roger J. W. Truscott, Michael J. Davies

Research output: Contribution to journalConference paperResearchpeer-review

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.

Fingerprint

Crystallins
Metabolites
Tryptophan
Cataract
Lenses
Metal ions
3-Hydroxyanthranilic Acid
Metals
Ions
Transition metals
Proteins
Wavelength
Oxidation
Photosensitizing Agents
Molecular mass
Solar radiation
Ultraviolet radiation
Oxidation-Reduction
Aging of materials
Radiation

Keywords

  • Cataract
  • lens
  • metal ions
  • 3-hydroxykynurenine
  • crosslinking
  • protein oxidation

Cite this

Tweeddale, Helen J. ; Hawkins, Clare L. ; 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.
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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.",
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language = "English",
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journal = "Free Radical Research",
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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 L.; 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 journalConference paperResearchpeer-review

TY - JOUR

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

T2 - Free Radical Research

AU - Tweeddale,Helen J.

AU - Hawkins,Clare L.

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.

KW - Cataract

KW - lens

KW - metal ions

KW - 3-hydroxykynurenine

KW - crosslinking

KW - protein oxidation

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U2 - 10.1080/10715762.2016.1210802

DO - 10.1080/10715762.2016.1210802

M3 - Conference paper

VL - 50

SP - 1116

EP - 1130

JO - Free Radical Research

JF - Free Radical Research

SN - 1071-5762

IS - 10

ER -