Carnosine Inhibits (E)-4-Hydroxy-2-nonenal-Induced Protein Cross-Linking: Structural Characterization of Carnosine-HNE Adducts1

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• 作者：Yahua Liu ; Guozhang Xu ; and Lawrence M. Sayre
• 刊名：Chemical Research in Toxicology
• 出版年：2003
• 出版时间：December 2003
• 年：2003
• 卷：16
• 期：12
• 页码：1589 - 1597
• 全文大小：184K
• 年卷期：v.16,no.12(December 2003)
• ISSN：1520-5010

文摘

(E)-4-Hydroxy-2-nonenal (HNE) is a highly cytotoxic aldehyde generated during peroxidationof lipids, which induces modification and aggregation of low-density lipoproteins and has beenfound 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 beaugmented 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 isolatedand structurally characterized. The main carnosine-HNE adduct is shown to be a 13-membercyclic adduct formed through initial Schiff base formation followed by conjugate addition ofthe imidazole group.