Rate of formation of AGEs during ascorbate glycation and during aging in human lens tissue

Cheng, Rongzhu; Lin, Bin; Ortwerth, B.J.

doi:10.1016/s0925-4439(02)00069-8

Cited by 37 publications

(34 citation statements)

References 31 publications

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“…8). The same pattern of human lens coloration (27) the increases of other post-translational modifications of lens proteins, e.g. by UV filters (35-37) after middle age have been previously reported.…”

Section: Discussionsupporting

confidence: 83%

Structure Elucidation of a Novel Yellow Chromophore from Human Lens Protein

Cheng

Argirov

et al. 2004

Journal of Biological Chemistry

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We report here the isolation of a novel acid-labile yellow chromophore from the enzymatic digest of human lens proteins and the identification of its chemical structure by liquid chromatography-mass spectrometry, liquid chromatography-tandem mass spectrometry, and 1 H, 13 C, and two-dimensional NMR. This new chromophore exhibited a UV absorbance maximum at 343 nm and fluorescence at 410 nm when excited at 343 nm. Analysis of the purified compound by reversed-phase HPLC with in-line electrospray ionization mass spectrometry revealed a molecular mass of 370 Da. One-and two-dimensional NMR analyses elucidated the structure to be 1-(5-amino-5-carboxypentyl)-4-(5-amino-5-carboxypentylamino)-3-hydroxy-2,3-dihydropyridinium, a cross-link between the ⑀-amino groups of two lysine residues, and a five-carbon ring. Because this cross-link contains two lysine residues and a dihydropyridinium ring, we assigned it the trivial name of K2P. Quantitative determinations of K2P in individual normal human lens or cataract lens water-soluble and water-insoluble protein digests were made using a high-performance liquid chromatograph equipped with a diode array detector. These measurements revealed a significant enhancement of K2P in cataract lens proteins (613 ؎ 362 pmol/mg of water-insoluble sonicate supernatant (WISS) protein or 85 ؎ 51 pmol/mg of WS protein) when compared with aged normal human lens proteins (261 ؎ 93 pmol/mg of WISS protein or 23 ؎ 15 pmol/mg of watersoluble (WS) protein). These data provide chemical evidence for increased protein cross-linking during aging and cataract development in vivo. This new cross-link may serve as a quantitatively more significant biomarker for assessing the role of lens protein modifications during aging and in the pathogenesis of cataract.The aging of human lens is characterized by increasing levels of water-insoluble (WI) 1 proteins in association with high levels of yellow chromophores and non-tryptophan fluorescence (1-4). These biochemical changes are all enhanced in senile and brunescent cataractous lenses. Glycation of lens proteins has been suggested to be a major protein modification in older lenses, and indeed diabetic patients have an increased risk of cataract formation (5). The human lens is largely composed of elongated fiber cells that are derived from epithelial cells located in a thin layer on the anterior surface. The innermost layers of the lens are formed during embryonic development and remain throughout life (6). Due to the lifelong stability of the lens crystallins, they can continuously accumulate damaging modifications. In time, these modifications may be responsible for the protein aggregation and protein cross-linking seen in age-onset cataracts (7-9). Furthermore, a dramatic, visible increase in protein-bound chromophores occurs during brunescent cataract formation, especially in tropical countries (10, 11). However, the chemical mechanisms responsible for the development of lens coloration and cataract remain unknown.In the past two decades, enormous progres...

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Section: Discussionsupporting

confidence: 83%

Structure Elucidation of a Novel Yellow Chromophore from Human Lens Protein

Cheng

Argirov

et al. 2004

Journal of Biological Chemistry

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“…The process is greatly accelerated during cataractogenesis, and can become extreme in brunescent cataracts. Unequivocal evidence now points to a major role of AGEs in the age-related pigmentation and crosslinking of human lens crystallins (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Isolation, purification and characterization of histidino-threosidine, a novel Maillard reaction protein crosslink from threose, lysine and histidine

Dai¹,

Nemet²,

Shen³

et al. 2007

Archives of Biochemistry and Biophysics

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We isolated a novel acid-labile yellow chromophore from the incubation of lysine, histidine and Dthreose and identified its chemical structure by one and two-dimensional 1 H and DEPT NMR spectroscopy combined with LC-tandem mass spectrometry. This new cross-link exhibits a UV absorbance maximum at 305 nm and a molecular mass of 451 Da. The proposed structure is 2-amino-5-(3-((4-(2-amino-2-carboxyethyl)-1H-imidazol-1-yl)methyl)-4-(1,2-dihydroxyethyl)-2-formyl-1H-pyrrol-1-yl)pentatonic acid, a cross-link between lysine and histidine with addition of two threose molecules. It was in part deduced and confirmed through synthesis of the analogous compound from n-butylamine, imidazole and D-threose. We assigned the compound the trivial name histidino-threosidine. Systemic incubation revealed that histidino-threosidine can be formed in low amounts from fructose, glyceraldehyde, methylglyoxal, glycolaldehyde, ascorbic acid, and dehydroascorbic acid, but at a much higher yield with degradation products of ascorbic acid, i.e. threose, erythrose, and erythrulose. Bovine lens protein incubated with 10 and 50 mM threose for two weeks yielded 560 and 2840 pmol/mg histidino-threosidine. Histidino-threosidine is to our knowledge the first Maillard reaction product known to involve histidine in a crosslink.

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“…Human lens proteins undergo numerous chemical changes with age, and this process is accelerated in cataractogenesis (1)(2)(3). One of the most prominent features of this process is pigmentation (1, 2, 4 -6).…”

mentioning

confidence: 99%

“…One of the most prominent features of this process is pigmentation (1, 2, 4 -6). Yellowish and brown pigments accumulate throughout the lens during aging, but they appear denser at the lens nucleus (2,4,7). In senile cataractous lenses, these pigments appear even deeper in color.…”

mentioning

confidence: 99%

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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Rate of formation of AGEs during ascorbate glycation and during aging in human lens tissue

Cited by 37 publications

References 31 publications

Structure Elucidation of a Novel Yellow Chromophore from Human Lens Protein

Structure Elucidation of a Novel Yellow Chromophore from Human Lens Protein

Isolation, purification and characterization of histidino-threosidine, a novel Maillard reaction protein crosslink from threose, lysine and histidine

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

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