Carnosine protects against the inactivation of esterase induced by glycation and a steroid

Abstract

Carnosine, an endogenous histidine-containing dipeptide, protects protein from oxidation and glycation, which may contribute to a potential treatment for some conformational diseases including cataract. Glycation, the non-enzymic reaction of sugars with proteins, promotes cross-linking and further aggregation. Prolonged use of glucocorticoids is a risk factor for cataract, as is diabetes. Esterase activity in the lens is decreased in senile cataract and diabetes. Previously, we reported that glycation and a steroid inactivate esterase. Here we tested the inactivation of esterase with fructose, fructose 6-phosphate (F6P) and ribose as model glycation reactions and prednisolone-21-hemisuccinate (P-21-H) as a model steroid and investigated the ability of carnosine to protect esterase against inactivation. The activity of esterase was measured by a spectrophotometric assay using p-nitrophenyl acetate as the substrate. The modified esterase was examined electrophoretically. The esterase was progressively inactivated by F6P, fructose, ribose and P-21-H. P-21-H was more effective than the sugars. Carnosine significantly inhibited the inactivation of esterase induced by all four compounds. Carnosine decreased the extent of the cross-linking. These results provide further evidence for carnosine's role as an anti-glycation compound. It is also proposed that carnosine may be an anti-steroid agent.

Protection of Proteins from Oxidative Stress: A New Illusion or a Novel Strategy?

“…The protective effect of MDA was explained by ability of carnosine to interact with aldehydes and ketones 11. This suggestion was confirmed very recently by other investigators 28…”

Transcriptome of the GSH-Depleted Lens Reveals Changes in Detoxification and EMT Signaling Genes, Transport Systems, and Lipid Homeostasis

“…Interestingly, it has been found that carboxylesterase activity in the lens decreases steadily with age due to glycation of the enzyme, 44 indicating a possible role in human cataract.…”

Carnosine Prevents Apoptosis of Glomerular Cells and Podocyte Loss in STZ Diabetic Rats

“…biochemical properties of carnosine, i.e. antioxidant effects and inhibition of AGE formation [22,24,[39][40][41][42], we expected that carnosine feeding would counteract these factors in kidneys of diabetic rats. Yet surprisingly, our results clearly show that carnosine feeding of diabetic rats is neither capable of preventing oxidative stress and AGE formation, nor could carnosine prevent the activation of the hexosamine pathway in our experimental setting, despite of carnosine feeding significantly increased renal carnosine concentrations.…”