Maillard Reactions in Lens Proteins: Methylglyoxal-mediated Modifications in the Rat Lens

doi:10.1006/exer.1999.0800

Experimental Eye Research

Volume 70, Issue 3, March 2000, Pages 369-380

https://doi.org/10.1006/exer.1999.0800 Get rights and content

Abstract

The nonenzymatic Maillard reaction is thought to contribute to aging and cataract formation in the lens. As levels of methylglyoxal (MG) and glutathione (GSH) affect the reaction, we examined the relationship of these factors and determined the effect of a glyoxalase I inhibitor on the Maillard reaction. Rat lens cultures were maintained for up to 3 days in TC-199 medium with or without 20 m $m$ glyceraldehyde (GLD) and 250 μ $m$ S-[N-hydroxy-N-(4-chlorophenyl) carbamoyl] glutathione diethyl ester (HCCG diester). We measured GSH, MG, D-lactate, glyoxalase I activity, immunoreactive MG-derived advanced glycation endproducts (MG-AGEs) and imidazolysine in organ cultured rat lenses. In vitro experiments with isolated rat lens proteins revealed that HCCG alone inhibited glyoxalase I activity in a dose-dependent manner. In organ cultured rat lens protein, GLD increased MG levels 24-fold, and the addition of HCCG diester further increased it by about two-fold. GSH levels fell sharply in the presence of GLD and this was prevented to some extent by the presence of HCCG diester. D-lactate production in the lens was suppressed by HCCG diester treatment. Dialysed lens proteins retained glyoxalase I activity, indicating that the enzyme was unaltered during incubation. MG-AGEs and imidazolysine levels were significantly higher (P<0.05) in GLD-treated lenses, but a combination of HCCG diester and GLD lowered immunoreactive MG-AGEs and imidazolysine levels compared to GLD alone. HCCG had no significant effect on MG-AGE formation in lens proteins incubated with GLD or MG. We conclude that exogenous GLD enhances MG and MG-AGE levels in the rat lens and that this increase is accompanied by a loss in GSH. In addition, inhibition of glyoxalase I promotes MG accumulation.

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^f1: Author for correspondence: Department of Ophthalmology, Case Western Reserve University, Wearn Bldg., Room 643, Cleveland, OH 44106, U.S.A. E-mail: [email protected]

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Regular articleMaillard Reactions in Lens Proteins: Methylglyoxal-mediated Modifications in the Rat Lens

Abstract

J. Biol. Chem.

Exp. Eye Res.

Adv. Pharmacol.

Arch. Biochem. Biophys.

Exp. Eye Res.

Exp. Eye Res.

Anal. Biochem.

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J. Biol. Chem.

Exp. Eye Res.

Arch. Biochem. Biophys.

Exp. Eye Res.

J. Biol. Chem.

J. Biol. Chem.

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J. Chromatograph.

Exp. Eye Res.

J. Biol. Chem.

Exp. Eye Res.

Biochem. Pharmacol.

Exp. Eye Res.

Biochim. et Biophys. Acta.

J. Biol. Chem.

Exp. Eye Res.

Exp. Eye Res.

Mol. Asp. Med.

FEBS Letts.

J. Biol. Chem.

J. Biol. Chem.

N-epsilon-(carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins

Biochem. J.

Studies on human lenses: II. Distribution and solubility of fluorescent pigments in cataractous and non-cataractous lenses of Indian origin

Photochem. Photobiol.

Regular article
Maillard Reactions in Lens Proteins: Methylglyoxal-mediated Modifications in the Rat Lens