Carnosine Protects Proteins against Methylglyoxal-Mediated Modifications

Abstract

Methylglyoxal (MG) (pyruvaldehyde) is an endogenous metabolite which is present in increased concentrations in diabetics and implicated in formation of advanced glycosylation end-products (AGEs) and secondary diabetic complications. Carnosine (β-alanyl-L-histidine) is normally present in long-lived tissues at concentrations up to 20mM in humans. Previous studies showed that carnosine can protect proteins against aldehyde-containing cross-linking agents such as aldose and ketose hexose and triose sugars, and malondialdehyde, the lipid peroxidation product. Here we examine whether carnosine can protect protein exposed to MG. Our results show that carnosine readily reacts with MG thereby inhibiting MG-mediated protein modification as revealed electrophoretically. We also investigated whether carnosine could intervene when proteins were exposed to an MG-induced AGE (i.e. lysine incubated with MG). Our results show that carnosine can inhibit protein modification induced by a lysine-MG-AGE; this suggests a second intervention site for carnosine and emphasizes its potential as a possible non-toxic modulator of diabetic complications.