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*

*Corresponding author for this work

    Research output: Contribution to journalConference paperpeer-review

    22 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)1116-1130
    Number of pages15
    JournalFree Radical Research
    Volume50
    Issue number10
    DOIs
    Publication statusPublished - Oct 2016
    EventBiennial Meeting of Society for Free Radical Research Asis (7th : 2015): Advanced Oxidative Stress Research for Health Benefits and Well-beings - Chiang Mai, Thailand
    Duration: 29 Nov 20152 Dec 2015
    Conference number: 7th

    Keywords

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

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