Carnosine disaggregates glycated α-crystallin: an in vitro study

Abstract

Protein glycation, which promotes aggregation, involves the unwanted reaction of carbohydrate oxidation products with proteins. Glycation of lens α-crystallin occurs in vivo and may contribute to cataractogenesis. Anti-glycation compounds such as carnosine may be preventive, but interestingly carnosine reverses lens opacity in human trials. The mechanism for this observation may involve carnosine's ability to disaggregate glycated protein. We investigated this hypothesis using glycated α-crystallin as our in vitro model. Methylglyoxal-induced glycation of α-crystallin caused aggregation as evidenced by increased 90° light scattering. After addition of carnosine, light scattering returned to baseline levels suggesting that the size of the glycation-induced aggregates decreased. Additionally, carnosine decreased tryptophan fluorescence polarization of glycated α-crystallin, suggesting that carnosine increased peptide chain mobility, which may contribute to the controlled unfolding of glycated protein. Comparatively, guanidine–HCl and urea had no effect. Our data support the hypothesis that carnosine disaggregates glycated α-crystallin.