Methylglyoxal-derived hydroimidazolone advanced glycation end-products of human lens proteins.

Abstract

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 beta = 0.094, P = 0.026) and argpyrimidine (beta = 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.

• Authors: Naila Ahmed, Paul J Thornalley, Jens Dawczynski, Sybille Franke, Juergen Strobel, Günter Stein, George M Haik
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 44 Issue 12 Pg. 5287-92 (Dec 2003) ISSN: 0146-0404 [Print] United States
• PMID: 14638728 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Crystallins
• Glycation End Products, Advanced
• Imidazoles
• imidazolone
• Pyruvaldehyde
• Arginine
• pentosidine
• Lysine

Topics

• Aged
• Arginine (analogs & derivatives)
• Cataract (metabolism)
• Chromatography, High Pressure Liquid
• Crystallins (chemistry)
• Female
• Fluorometry
• Glycation End Products, Advanced (analysis)
• Humans
• Hydrolysis
• Imidazoles (analysis)
• Lens, Crystalline (chemistry)
• Lysine (analogs & derivatives)
• Male
• Mass Spectrometry
• Middle Aged
• Pyruvaldehyde (analysis)