Carnosine inhibits (E)-4-hydroxy-2-nonenal-induced protein cross-linking: structural characterization of carnosine-HNE adducts.
(E)-4-Hydroxy-2-nonenal (HNE) is a highly cytotoxic aldehyde generated during peroxidation of lipids, which induces modification and aggregation of low-density lipoproteins and has been found to elicit covalent cross-linking of proteins. Carnosine was previously shown to trap HNE. Results presented here provide evidence that by trapping HNE in stable covalent adducts, carnosine can inhibit HNE-induced protein cross-linking. This trapping effect may be augmented by carnosine-chelating trace transition metal ions that promote oxidative HNE-induced cross-linking. Adducts formed in the reaction of HNE with carnosine have been isolated and structurally characterized. The main carnosine-HNE adduct is shown to be a 13-member cyclic adduct formed through initial Schiff base formation followed by conjugate addition of the imidazole group.
Liu
Yahua
Y
Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Xu
Guozhang
G
Sayre
Lawrence M
LM
D000447:Aldehydes / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D002336:Carnosine / Q000737:chemistry* / Q000494:pharmacology*; D002417:Cattle; D002614:Chelating Agents / Q000494:pharmacology; D019327:Copper Sulfate / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology; D006146:Guanidines / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010179:Pancreas / Q000201:enzymology; D004369:Pentetic Acid / Q000494:pharmacology; D012259:Ribonuclease, Pancreatic / Q000737:chemistry
D000447:Aldehydes; D002614:Chelating Agents; D003432:Cross-Linking Reagents; D006146:Guanidines; D004369:Pentetic Acid; D002336:Carnosine; D012259:Ribonuclease, Pancreatic; C027576:4-hydroxy-2-nonenal; D019327:Copper Sulfate; C004479:pimagedine