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Methylglyoxal-Derived Hydroimidazolone Advanced Glycation End-Products of Human Lens Proteins

¹From the Department of Biological Sciences, University of Essex, Colchester, United Kingdom; ²Departments of Ophthalmology and ³Internal Medicine IV, Friedrich Schiller University, Jena, Germany; and ⁴George Haik Eye Clinic, New Orleans, Louisiana.

PURPOSE. To determine the concentrations of methylglyoxal-derived advanced glycation end-products (AGEs), the hydroimidazolones MG-H1 and -H2, in soluble human lens proteins and compare them with the concentrations of other methylglyoxal-derived AGEs and pentosidine.

METHODS. Lens protein samples were hydrolyzed enzymatically. AGEs were assayed without derivatization by HPLC with tandem mass spectrometry; the fluorescent AGEs argpyrimidine and pentosidine were assayed by fluorometric detection. MG-H1 and -H2 were resolved and assayed by fluorometric detection after derivatization with 6-aminoquinolyl-N-hydroxysuccimidylcarbamate (AQC).

RESULTS. The methylglyoxal-derived hydroimidazolones MG-H1 and -H2 were detected and quantified in human lens proteins. AGE concentrations (mean ± SEM) were: MG-H1 4609 ± 411 pmol/mg protein, MG-H2 3085 ± 328 pmol/mg protein, argpyrimidine 205 ± 19 pmol/mg protein, and pentosidine 0.693 ± 0.104 pmol/mg protein. The concentration of MG-H1 in human lens protein correlated positively with donor age (correlation coefficient = 0.28, P < 0.05), the concentration of MG-H2 (correlation coefficient = 0.78, P < 0.001) and argpyrimidine (correlation coefficient = 0.42, P < 0.01). The concentrations of AGEs were increased in cataractous lenses in comparison with noncataractous lenses: the increases were MG-H1 85%, MG-H2 122%, argpyrimidine 255%, and pentosidine 183% (P < 0.001). Multiple logistic regression analysis showed a significant link of cataract to donor age (regression coefficient ß = 0.094, P = 0.026) and argpyrimidine (ß = 0.022, P = 0.002).

CONCLUSIONS. Methylglyoxal hydroimidazolones are quantitatively major AGEs of human lens proteins. These substantial modifications of lens proteins may stimulate further glycation, oxidation, and protein aggregation leading to the formation of cataract.

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