Pluripotent protective effects of carnosine, a naturally occurring dipeptide

被引:145
作者
Hipkiss, AR [1 ]
Preston, JE
Himsworth, DTM
Worthington, VC
Keown, M
Michaelis, J
Lawrence, J
Mateen, A
Allende, L
Eagles, PAM
Abbott, NJ
机构
[1] Univ London Kings Coll, Mol Biol & Biophys Grp, London WC2R 2LS, England
[2] Univ London Kings Coll, Inst Gerontol, London WC2R 2LS, England
[3] Univ London Kings Coll, Dept Physiol, London WC2R 2LS, England
[4] CSIRO, Div Biomol Engn, Sydney, NSW 2112, Australia
[5] Peptide Technol Ltd, Sydney, NSW 2099, Australia
来源
TOWARDS PROLONGATION OF THE HEALTHY LIFE SPAN: PRACTICAL APPROACHES TO INTERVENTION | 1998年 / 854卷
关键词
D O I
10.1111/j.1749-6632.1998.tb09890.x
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Carnosine is a naturally occurring dipeptide (beta-alanyl-L-histidine) found in brain, innervated tissues, and the lens at concentrations up to 20 mM in humans. In 1994 it was shown that carnosine could delay senescence of cultured human fibroblasts, Evidence will be presented to suggest that carnosine, in addition to antioxidant and oxygen free-radical scavenging activities, also reacts with deleterious aldehydes to protect susceptible macromolecules, Our studies show that, in vitro, carnosine inhibits nonenzymic glycosylation and cross-linking of proteins induced by reactive aldehydes (aldose and ketose sugars, certain triose glycolytic intermediates and malondialdehyde (MDA), a lipid peroxidation product). Additionally we show that carnosine inhibits formation of MDA-induced protein-associated advanced glycosylation end products (AGEs) and formation of DNA-protein cross-links induced by acetaldehyde and formaldehyde. At the cellular level 20 mM carnosine protected cultured human fibroblasts and lymphocytes, CHO cells, and cultured rat brain endothelial cells against the toxic effects of formaldehyde, acetaldehyde and MDA, and AGEs formed by a lysine/deoxyribose mixture. Interestingly, carnosine protected cultured rat brain endothelial cells against amyloid peptide toxicity. We propose that carnosine (which is remarkably nontoxic) or related structures should be explored for possible intervention in pathologies that involve deleterious aldehydes, for example, secondary diabetic complications, inflammatory phenomena, alcoholic liver disease, and possibly Alzheimer's disease.
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页码:37 / 53
页数:17
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