Mechanism of lysine oxidation in human lens crystallins during aging and in diabetes

Xingjun Fan, Jianye Zhang, Matilde Theves, Christopher Strauch, Ina Nemet, Xiaoqin Liu, Juna Qian, Frank J. Giblin, Vincent M. Monnier

Research output: Contribution to journalArticle

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Abstract

Oxidative mechanisms during nuclear sclerosis of the lens are poorly understood, in particular metal-catalyzed oxidation. The lysyl oxidation product adipic semialdehyde (allysine, ALL) and its oxidized end-product 2-aminoadipic acid (2-AAA) were determined as a function of age and presence of diabetes. Surprisingly, whereas both ALL and 2-AAA increased with age and strongly correlated with cataract grade and protein absorbance at 350 nm, only ALL formation but not 2-AAA was increased by diabetes. To clarify the mechanism of oxidation, rabbit lenses were treated with hyperbaric oxygen (HBO) for 48 h, and proteins were analyzed by gas and liquid chromatography mass spectrometry for ALL, 2-AAA, and multiple glycation products. Upon exposure to HBO, rabbit lenses were swollen, and nuclei were yellow. Protein-bound ALL increased 8-fold in the nuclear protein fractions versus controls. A dramatic increase in methyl-glyoxal hydroimidazolone and carboxyethyl-lysine but no increase of 2-AAA occurred, suggesting more drastic conditions are needed to oxidize ALL into 2-AAA. Indeed the latter formed only upon depletion of glutathione and was catalyzed by H2O2. Neither carboxymethyl-lysine nor glyoxal hydroimidazolone, two markers of glyco-/lipoxidation, nor markers of lenticular glycemia (fructose-lysine, glucospane) were elevated by HBO, excluding significant lipid peroxidation and glucose involvement. The findings strongly implicate dicarbonyl/metal catalyzed oxidation of lysine to allysine, whereby low GSH combined with ascorbate-derived H2O2 likely contributes toward 2-AAA formation, since virtually no 2-AAA formed in the presence of methylglyoxal instead of ascorbate. An important translational conclusion is that chelating agents might help delay nuclear sclerosis.

Original languageEnglish (US)
Pages (from-to)34618-34627
Number of pages10
JournalJournal of Biological Chemistry
Volume284
Issue number50
DOIs
StatePublished - Dec 11 2009

Fingerprint

2-Aminoadipic Acid
Crystallins
Medical problems
Lenses
Lysine
Aging of materials
Oxidation
Glyoxal
Oxygen
Metals
Rabbits
Pyruvaldehyde
Proteins
Liquid chromatography
Sclerosis
Chelating Agents
Nuclear Proteins
allysine
Gas chromatography
Gas Chromatography-Mass Spectrometry

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Fan, X., Zhang, J., Theves, M., Strauch, C., Nemet, I., Liu, X., ... Monnier, V. M. (2009). Mechanism of lysine oxidation in human lens crystallins during aging and in diabetes. Journal of Biological Chemistry, 284(50), 34618-34627. https://doi.org/10.1074/jbc.M109.032094

Mechanism of lysine oxidation in human lens crystallins during aging and in diabetes. / Fan, Xingjun; Zhang, Jianye; Theves, Matilde; Strauch, Christopher; Nemet, Ina; Liu, Xiaoqin; Qian, Juna; Giblin, Frank J.; Monnier, Vincent M.

In: Journal of Biological Chemistry, Vol. 284, No. 50, 11.12.2009, p. 34618-34627.

Research output: Contribution to journalArticle

Fan, X, Zhang, J, Theves, M, Strauch, C, Nemet, I, Liu, X, Qian, J, Giblin, FJ & Monnier, VM 2009, 'Mechanism of lysine oxidation in human lens crystallins during aging and in diabetes', Journal of Biological Chemistry, vol. 284, no. 50, pp. 34618-34627. https://doi.org/10.1074/jbc.M109.032094
Fan, Xingjun ; Zhang, Jianye ; Theves, Matilde ; Strauch, Christopher ; Nemet, Ina ; Liu, Xiaoqin ; Qian, Juna ; Giblin, Frank J. ; Monnier, Vincent M. / Mechanism of lysine oxidation in human lens crystallins during aging and in diabetes. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 50. pp. 34618-34627.
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