Tryptophan Metabolites from Young Human Lenses and the Photooxidation of Ascorbic Acid by UVA Light

Ortwerth, B.J.; Bhattacharyya, Jaya; Shipova, Ekaterina V.

doi:10.1167/iovs.08-2927

Cited by 16 publications

(16 citation statements)

References 43 publications

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“…Lens receives UV light (UVA and UVB) through the cornea. It is known that kynurenines are photosensitizers and they can oxidize ascobate [46]. Whether such oxidation occurs in low oxygen environment is not known, but it is likely.…”

Section: Discussionmentioning

confidence: 99%

Modulation of advanced glycation endproduct synthesis by kynurenines in human lens proteins

Nagaraj

Padmanabha

Mailankot

et al. 2010

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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Human lens proteins (HLP) become chemically modified by kynurenines and advanced glycation end products (AGEs) during aging and cataractogenesis. We investigated the effects of kynurenines on AGE synthesis in HLP. We found that incubation with 5 mM ribose or 5 mM ascorbate produced significant quantities of pentosidine, and this was further enhanced in the presence of two different kynurenines (200-500 µM): N-formylkynurenine (Nfk) and kynurenine (Kyn). Another related compound, 3-hydroxykynurenine (3OH-Kyn), had disparate effects; low concentrations (10-200 µM) promoted pentosidine synthesis, but high concentrations (200-500 µM) inhibited it. 3OH-Kyn showed similar effects on pentosidine synthesis from Amadori-enriched HLP or ribated lysine. Chelex-100 treatment of phosphate buffer reduced pentosidine synthesis from Amadori-enriched HLP by ~90%, but it did not inhibit the stimulating effect of 3OH-Kyn and EDTA. 3OH-Kyn (100-500 µM) spontaneously produced copious amounts of H 2 O 2 (10-25 µM), but externally added H 2 O 2 had only a mild stimulating effect on pentosidine but had no effect on N ε -carboxymethyl lysine (CML) synthesis in HLP from ribose and ascorbate. Further, human lens epithelial cells incubated with ribose and 3OH-Kyn showed higher intracellular pentosidine than cells incubated with ribose alone. CML synthesis from glycating agents was inhibited 30 to 50% by 3OH-Kyn at concentrations of 100-500 µM. Argpyrimidine synthesis from 5 mM methylglyoxal was slightly inhibited by all kynurenines at concentrations of 100-500 µM. These results suggest that AGE synthesis in HLP is modulated by kynurenines, and such effects indicate a mode of interplay between kynurenines and carbohydrates important for AGE formation during lens aging and cataract formation.

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Section: Discussionmentioning

confidence: 99%

Modulation of advanced glycation endproduct synthesis by kynurenines in human lens proteins

Nagaraj

Padmanabha

Mailankot

et al. 2010

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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“…High-resolution magic angle spinning proton NMR spectroscopy of ocular tissues revealed that GSH is present at much higher concentrations in the lens (Kryczka et al, 2014). GSH can react with free radicals and other oxidants generated by the formation of singlet oxygen ( 1 O 2 ) from the interaction between ultraviolet photons and tryptophan residues on the proteins (Ortwerth et al, 2009) and can also react with the oxidized form of ascorbate, dehydroascorbate, to regenerate ascorbate (Sasaki et al, 1995). The resulting oxidized glutathione (GSSG) is reduced back to GSH by NADPH, produced by residual metabolic activity (the pentose phosphate shunt) in the lens (Ganea and Harding, 2006).…”

Section: Antioxidants and Other Oxidation Limiting Mechanisms In The mentioning

confidence: 99%

Small molecules, both dietary and endogenous, influence the onset of lens cataracts

Barnes

Quinlan

2017

Experimental Eye Research

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How the lens ages successfully is a lesson in biological adaption and the emergent properties of its complement of cells and proteins. This living tissue contains some of the oldest proteins in our bodies and yet they remain functional for decades, despite exposure to UV light, to reactive oxygen species and all the other hazards to protein function. This remarkable feat is achieved by a shrewd investment in very stable proteins as lens crystallins, by providing a reservoir of ATP-independent protein chaperones unequalled by any other tissue and by an oxidation-resistant environment. In addition, glutathione, a free radical scavenger, is present in mM concentrations and the plasma membranes contain oxidation-resistant sphingolipids, so what compromises lens function as it ages? In this review, we examine the role of small molecules in the prevention or causation of cataracts, including those associated with diet, metabolic pathways and drug therapy (steroids).

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“…The part of the solar spectrum that reaches and becomes absorbed by lens is thus dominated by UVA and the short wavelength segment of the visible spectrum. Whereas the detrimental effect of UVB is well documented in the literature, UVA seems less damaging [7,15,27] and may even bleach lens chromophores [28,29]. The effects of irradiation with visible light have not been described in the literature but since the aged human lens absorbs a great proportion of short wavelength visible light it is very relevant to examine this part of the electromagnetic spectrum for potentially hazardous effects.…”

Section: Introductionmentioning

confidence: 99%

Optical effects of exposing intact human lenses to ultraviolet radiation and visible light

et al. 2011

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BackgroundThe human lens is continuously exposed to high levels of light. Ultraviolet radiation is believed to play a causative role in the development of cataract. In vivo, however, the lens is mainly exposed to visible light and the ageing lens absorbs a great part of the short wavelength region of incoming visible light. The aim of the present study was to examine the optical effects on human lenses of short wavelength visible light and ultraviolet radiation.MethodsNaturally aged human donor lenses were irradiated with UVA (355 nm), violet (400 and 405 nm) and green (532 nm) lasers. The effect of irradiation was evaluated qualitatively by photography and quantitatively by measuring the direct transmission before and after irradiation. Furthermore, the effect of pulsed and continuous laser systems was compared as was the effect of short, intermediate and prolonged exposures.ResultsIrradiation with high intensity lasers caused scattering lesions in the human lenses. These effects were more likely to be seen when using pulsed lasers because of the high pulse intensity. Prolonged irradiation with UVA led to photodarkening whereas no detrimental effects were observed after irradiation with visible light.ConclusionsIrradiation with visible light does not seem to be harmful to the human lens except if the lens is exposed to laser irradiances that are high enough to warrant thermal protein denaturation that is more readily seen using pulsed laser systems.

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Tryptophan Metabolites from Young Human Lenses and the Photooxidation of Ascorbic Acid by UVA Light

Abstract: The filter compounds present in human lenses can absorb UVA light and cause the oxidation of ascorbic acid in the presence and absence of oxygen, possibly initiating the glycation of lens proteins.

Cited by 16 publications

References 43 publications

Modulation of advanced glycation endproduct synthesis by kynurenines in human lens proteins

Modulation of advanced glycation endproduct synthesis by kynurenines in human lens proteins

Small molecules, both dietary and endogenous, influence the onset of lens cataracts

Optical effects of exposing intact human lenses to ultraviolet radiation and visible light

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