Inhibition of Methylglyoxal-Mediated Protein Modification in Glyoxalase I Overexpressing Mouse Lenses

الملخص EN

Objective.

Here we tested the role of Glo I in the prevention of advanced glycation end product (AGE) formation in transgenic mouse lenses.

Methods.

A transgenic animal line that expressed high levels of human Glo I in the lens was developed from the C57B6 mouse strain.

The role of Glo I in the inhibition of MGO-AGE formation was tested in organ-cultured lenses.

Results.

Organ culture of Wt and Glo I lenses with 5 mM D, L-glyceraldehyde (GLD) enhanced MGO by 29-fold and 17-fold in Wt lenses and Glo I lenses, respectively.

Argpyrimidine levels were 192±73 pmoles/mg protein, and hydroimidazolone levels were 22±0.7 units/μg protein in GLD-incubated Wt lenses.

In Glo I lenses, formation of AGEs was significantly inhibited; the argpyrimidine levels were 82±18 pmoles/mg protein, and the HI levels were 2.6±2.3 units/μg protein.

Incubation of Wt lens proteins with 5 mM ribose for 7 days resulted in the formation of pentosidine.

However, the levels were substantially higher in Glo I lens proteins incubated with ribose.

Conclusion.

Our study provides direct evidence that Glo I activity plays an important role in the regulation of AGE synthesis in the lens; while Glo I activity blocks the formation of MGO-AGEs, it might promote the formation of sugar-derived AGEs.