 | TOWARDS PROLONGATION OF THE HEALTHY LIFE SPAN: Practical Approaches to Intervention
Copyright © 1998 by the New York Academy of Sciences
description
Annals of the New York Academy of Sciences 854:37-53 (1998)
© 1998 New York Academy of Sciences
Pluripotent Protective Effects of Carnosine, a Naturally Occurring Dipeptidea
A. R. HIPKISSb,e,g,
J. E. PRESTONc,
D.T. M. HIMSWORTHb,
V. C. WORTHINGTONb,
M. KEOWNb,
J. MICHAELISf,
J. LAWRENCEb,
A. MATEENb,
L. ALLENDEb,
P.A. M. EAGLESb AND
N. JOAN ABBOTTd
bMolecular Biology and Biophysics Group, King's College London, Strand, London WC2R 2LS, United Kingdom
cInstitute of Gerontology, King's College London, Strand, London WC2R 2LS, United Kingdom
dDepartment of Physiology, King's College London, Strand, London WC2R 2LS, United Kingdom
eDivision of Biomolecular Engineering, CSIRO North Ryde, Sydney, NSW 2112, Australia
fPeptide Technology Ltd., Dee Why, Sydney, NSW 2099, Australia
aThis work was supported by the World Cancer Research Fund.
gTel: 44.0171-873-2490; fax: 44. 0171-873-2285; e-mail: alan.hipkiss{at}kcl.ac.uk
Carnosine is a naturally occurring dipeptide (ß-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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