title: 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.
authors.affiliation: Nuffield Laboratory of Ophthalmology, University of Oxford, Walton St., Oxford OX2 6AW, UK.
authors.forename: Hong
authors.initials: H
authors.lastname: Yan
authors.forename: John J
authors.initials: JJ
authors.lastname: Harding
mesh_terms: D000818:Animals; D043182:Carboxylesterase / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D002336:Carnosine / Q000378:metabolism* / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005632:Fructose / Q000494:pharmacology; D005636:Fructosephosphates / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects*; D008099:Liver / Q000201:enzymology; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012266:Ribose / Q000494:pharmacology; D013256:Steroids / Q000494:pharmacology*; D013552:Swine; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D005636:Fructosephosphates; D017127:Glycation End Products, Advanced; D013256:Steroids; D005632:Fructose; C027618:fructose-6-phosphate; D012266:Ribose; D002336:Carnosine; D011239:Prednisolone; D043182:Carboxylesterase; C021322:prednisolone hemisuccinate