Naslov
Metal catalyzed oxidation of human lens proteins: effects of age, diabetes and oxygen

Autori
Fan, Xingjun ; Giblin, F H ; Zhang, Jianye ; Theves, Mathilde ; Strauch, Christopher ; Liu, Jie ; Qian, J ; Nemet, Ina ; Monnier, Vincent M.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
10th International Symposium on the Maillard Reaction / - Palm Cove : The Royal Society of Chemistry, 2009, 32-32

Skup
10th International Symposium on the Maillard Reaction

Mjesto i datum
Cairns, Australija, 29.08.2009. - 01.09.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
human lens crystallins; deamination; deamidation; glycation; oxidation; lipid peroxidation

Sažetak
Human lens crystallins accumulate damage with age. Protein deami(n/d)ation, truncation, glycation, oxidation, and kynurenination are associated with enhanced risk of cataracts. We hypothesized that lysine residues undergo metal catalyzed oxidation (MCO) to the protein carbonyl allysine (ALL), then further oxidizes into 2-aminoadipic acid (2-AAA). (Biochem. J. 2007, 404:269). We determine both products in fractions of human lenses to hyperbaric oxygen. Methods: 55 lenses (age range 6-79 yrs, 22 diabetic), were separated into soluble and insoluble fractions and reduced with NaBH4 to convert allysine into 6-hydroxynorleucine (6OHLNL). AGEs were measured in acid hydrolysates by SIM-GC-MS. Rabbit lenses (n=6 per group) Results: Both ALL and 2-AAA increased with age in both fractions. Levels strongly correlated with PIRIE cataract grade and protein chromophores at 350 nm. Diabetes catalyzed ALL formation but surprisingly not 2-AAA. Hyperbaric O2 treated rabbit lenses were swollen with yellow nuclei. ALL increased 8- and 4-fold (p<0.0001) in the WS (N) and (C) fractions, respectively, vs. controls. Dramatic increase in methylglyoxal hydroimidazolone (MG-H1) resulted resulted from hyp-O2, with a six-fold elevation in C (p<0.05) and a 50%increase in N (p=NS). CEL, another MG-derived product, also increased in both WS and WI fractions (20 and 100%, respectively, p<0.05). Surprisingly, no increase of 2-AAA occurred suggesting drastic conditions are needed to oxidize ALL into 2-AAA. Neither CML and G-H1, two markers of lipid peroxidation, nor markers of lenticular glycemia (fructose-lysine, glucospane) were elevated, excluding significant lipo- and glycoxidation. The discovery that oxidative deamination progress in the aging and diabetic human lens is novel and implies catalytic metals. The data strongly implicate MCO, whereby hyp-O2 likely oxidizes ascorbate (ASA) to DHA and MG, which then binds to lysyl residues to form a Cu2+ complex leading to oxidative deamination of lysine. Interestingly, the fact that further oxidation of allysine to 2-AAA was modest in lens compared to sking suggest that the lens maintains a strong reducing environment.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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