Protein-Bound UV Filters in Normal Human Lenses: The Concentration of Bound UV Filters Equals That of Free UV Filters in the Center of Older Lenses

Korlimbinis, Anastasia; Aquilina, J. Andrew; Truscott, Roger J.W.

doi:10.1167/iovs.06-1134

Cited by 35 publications

(40 citation statements)

References 27 publications

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“…Whereas the Kyn levels in the wild type mouse lens were 0.0028 Ϯ 0.001 nmol/mg wet weight, our data show that it was ϳ250-fold higher (0.71 Ϯ 0.14 nmol/mg wet weight) in the lens of the double-transgenic mouse (Fig. 3B), which is similar to the levels of Kyn in human lenses (57,62).…”

Section: Asc Oxidation By Uva Photolysis Of Lmw Fraction Of Hido/ Hsvct2supporting

confidence: 67%

UVA Light-excited Kynurenines Oxidize Ascorbate and Modify Lens Proteins through the Formation of Advanced Glycation End Products

Linetsky

Raghavan

Johar³

et al. 2014

Journal of Biological Chemistry

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Background: Human lens proteins accumulate pigmented, protein-cross-linked AGE adducts during cataract formation, and the mechanisms of their formation are poorly understood. Results: UVA-excited kynurenines can oxidize ascorbate under anoxic conditions and promote synthesis of AGEs. Conclusion: UVA light-excited kynurenines promote AGE synthesis and contribute to cataract formation. Significance: This study provides a mechanism for UVA light-mediated damage to lens proteins during cataract formation.

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Section: Asc Oxidation By Uva Photolysis Of Lmw Fraction Of Hido/ Hsvct2supporting

confidence: 67%

UVA Light-excited Kynurenines Oxidize Ascorbate and Modify Lens Proteins through the Formation of Advanced Glycation End Products

Linetsky

Raghavan

Johar³

et al. 2014

Journal of Biological Chemistry

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“…However, the depletion of GSH in aging and cataractous lenses could shift the balance toward the adduction of kynurenines to proteins (12). This notion is supported by findings indicating that the levels of kynurenine-adducted proteins increase with lens age and severity of cataract formation (22,24,25).…”

mentioning

confidence: 81%

“…Kynurenines are perceived to be UV filters in the lens. However, kynurenines undergo spontaneous deamination to form ␣,␤-unsaturated ketones that can react with nucleophilic amino acids in lens proteins and GSH (21,22). The reaction with GSH is probably a mechanism that restricts the damaging effects of kynurenines because the latter can react with lens proteins to form adducts that can cross-link proteins (23).…”

mentioning

confidence: 99%

Identification of Kynoxazine, a Novel Fluorescent Product of the Reaction between 3-Hydroxykynurenine and Erythrulose in the Human Lens, and Its Role in Protein Modification

Rakete

Nagaraj

2016

Journal of Biological Chemistry

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Kynurenine pathway metabolites and ascorbate degradation products are present in human lenses. In this study, we showed that erythrulose, a major ascorbate degradation product, reacts spontaneously with 3-hydroxykynurenine to form a fluorescent product. Structural characterization of the product revealed it to be 2-amino-4-(2-hydroxy-3-(2-hydroxyethyl)-2H-benzo[b][1, 4]oxazin-5-yl)-4-oxobutanoic acid, which we named kynoxazine. Unlike 3-hydroxykynurenine, 3-hydroxykynurenine glucoside and kynurenine were unable to form a kynoxazine-like compound, which suggested that the aminophenol moiety in 3-hydroxykynurenine is essential for the formation of kynoxazine. This reasoning was confirmed using a model compound, 1-(2-amino-3-hydroxyphenyl)ethan-1-one, which is an aminophenol lacking the amino acid moiety of 3-hydroxykynurenine. Ultra-performance liquid chromatography-tandem mass spectrometry analyses showed that kynoxazine is present in the human lens at levels ranging from 0 to 64 pmol/mg lens. Kynoxazine as well as erythrulose degraded under physiological conditions to generate 3-deoxythreosone, which modified and cross-linked proteins through the formation of an arginine adduct, 3-deoxythreosone-derived hydroimidazolone, and a lysine-arginine cross-linking adduct, 3-deoxythreosone-derived hydroimidazolimine cross-link. Ultra-performance liquid chromatography-tandem mass spectrometry quantification showed that 32-169 pmol/mg protein of 3-deoxythreosone-derived hydroimidazolone and 1.1-11.2 pmol/mg protein of 3-deoxythreosone-derived hydroimidazolimine cross-link occurred in aging lenses. Taken together, these results demonstrate a novel biochemical mechanism by which ascorbate oxidation and the kynurenine pathway intertwine, which could promote protein modification and cross-linking in aging human lenses.

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“…Indeed, retinas of guinea pigs that have been made aphakic have been reported to be damaged by physiological levels of UVA light [17]. Similar events may occur in the aging human lens where the binding of the UVA chromophore kynurenine to crystallins may lead to subsequent generation of damaging ROS [18]. …”

Section: Introductionmentioning

confidence: 99%

Expression and purification of his-tagged recombinant mouse ζ-crystallin

Simpanya

Leverenz

Giblin

2010

Protein Expression and Purification

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Abstractζ-crystallin is an NADPH-binding protein consisting of four identical 35 kD subunits. The protein possesses quinone oxidoreductase activity, and is present in large amounts in the lenses of camelids, certain hystricomorphic rodents, and the Japanese tree frog, and in lower catalytic amounts in certain tissues of various species. In this study, recombinant methods were used to produce substantial quantities of his-tagged recombinant mouse ζ-crystallin, which was then purified to homogeneity. The yield of pure recombinant mouse ζ-crystallin was 5 times that obtained previously for purification of recombinant guinea pig ζ-crystallin. The quinone oxidoreductase activity of purified his-tagged recombinant mouse ζ-crystallin was comparable to that of purified native guinea pig lens ζ-crystallin, and to that previously reported for recombinant guinea pig ζ-crystallin. The method permits production of substantial amounts of recombinant ζ-crystallin for conducting studies on the biological role of this interesting protein, which exists in such high concentration in the lenses of certain species.

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Protein-Bound UV Filters in Normal Human Lenses: The Concentration of Bound UV Filters Equals That of Free UV Filters in the Center of Older Lenses

Cited by 35 publications

References 27 publications

UVA Light-excited Kynurenines Oxidize Ascorbate and Modify Lens Proteins through the Formation of Advanced Glycation End Products

UVA Light-excited Kynurenines Oxidize Ascorbate and Modify Lens Proteins through the Formation of Advanced Glycation End Products

Identification of Kynoxazine, a Novel Fluorescent Product of the Reaction between 3-Hydroxykynurenine and Erythrulose in the Human Lens, and Its Role in Protein Modification

Expression and purification of his-tagged recombinant mouse ζ-crystallin

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