Carnosine inhibits (E)-4-hydroxy-2-nonenal-induced protein cross-linking:: Structural characterization of carnosine-HNE adducts

被引：63

作者：

Liu, YH ^{[1
]}

Xu, GZ ^{[1
]}

Sayre, LM ^{[1
]}

机构：

[1] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA

来源：

CHEMICAL RESEARCH IN TOXICOLOGY | 2003年 / 16卷 / 12期

关键词：

D O I：

10.1021/tx034160a

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

(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.

引用

页码：1589 / 1597

页数：9