HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 40, 38384-38394, October 3, 2003

This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 278/40/38384    most recent M305099200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Culbertson, S. M. Articles by Ingold, Keith. U. Search for Related Content PubMed PubMed Citation Articles by Culbertson, S. M. Articles by Ingold, Keith. U. Social Bookmarking                      What's this?

Paradoxical Impact of Antioxidants on Post-Amadori Glycoxidation

COUNTERINTUITIVE INCREASE IN THE YIELDS OF PENTOSIDINE AND N-CARBOXYMETHYLLYSINE USING A NOVEL MULTIFUNCTIONAL PYRIDOXAMINE DERIVATIVE^*,

Sean M. Culbertson  , Ekaterina I. Vassilenko , Lisa D. Morrison ¶ and Keith. U. Ingold 

From the Steacie Institute for Molecular Sciences and the ^¶Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario K1A 0R6, Canada

The inhibition of post-Amadori advanced glycation end product (AGE) formation by three different classes of AGE inhibitors, carbonyl group traps, chelators, and radical-trapping antioxidants, challenge the current paradigms that: 1) AGE inhibitors will not increase the formation of any AGE product, 2) transition metal ions are required for oxidative formation of AGE, and 3) screening AGE inhibitors only in systems containing transition metal ions represents a valid estimate of potential in vivo mechanisms. This work also introduces a novel multifunctional AGE inhibitor, 6-dimethylaminopyridoxamine (dmaPM), designed to function as a combined carbonyl trap, metal ion chelator, and radical-trapping antioxidant. Other AGE inhibitors including pyridoxamine, aminoguanidine, o-phenylenediamine, dipyridoxylamine, and diethylenetriaminepentaacetic acid were also examined. The results during uninterrupted and interrupted ribose glycations show: 1) an unexpected increase in the yield of pentosidine in the presence of radical-trapping phenolic antioxidants such as Trolox and dmaPM, 2) significant formation of N-carboxymethyllysine (CML) in the presence of strong chelators and phenolic antioxidants, which implies that there must be nonradical routes to CML, 3) prevention of intermolecular cross-links with radical-trapping inhibitors, and 4) that dmaPM shows excellent inhibition of AGE. Glucose glycations reveal the expected inhibition of pentosidine and CML with all compounds tested, but in a buffer free of trace metal ions the yield of CML in the presence of radical-trapping antioxidants was between the metal ion-free and metal ion-containing controls. Protein molecular weight analyses support the conclusion that Amadori decomposition pathways are constrained in the presence of metal ion chelators and radical traps.

Received for publication, May 15, 2003 , and in revised form, July 10, 2003.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental material.

To whom correspondence should be addressed. Tel.: 613-991-5784; Fax: 613-952-0068; E-mail: sean.culbertson{at}nrc.ca.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. G. Huebschmann, J. G. Regensteiner, H. Vlassara, and J. E.B. Reusch Diabetes and Advanced Glycoxidation End Products. Diabetes Care, June 1, 2006; 29(6): 1420 - 1432. [Full Text] [PDF]

				J. M. Bohlender, S. Franke, G. Stein, and G. Wolf Advanced glycation end products and the kidney Am J Physiol Renal Physiol, October 1, 2005; 289(4): F645 - F659. [Abstract] [Full Text] [PDF]

				V. P. Reddy, M. R. Garrett, G. Perry, and M. A. Smith Carnosine: A Versatile Antioxidant and Antiglycating Agent Sci. Aging Knowl. Environ., May 4, 2005; 2005(18): pe12 - pe12. [Abstract] [Full Text]

				G. T. Mustata, M. Rosca, K. M. Biemel, O. Reihl, M. A. Smith, A. Viswanathan, C. Strauch, Y. Du, J. Tang, T. S. Kern, et al. Paradoxical Effects of Green Tea (Camellia Sinensis) and Antioxidant Vitamins in Diabetic Rats: Improved Retinopathy and Renal Mitochondrial Defects but Deterioration of Collagen Matrix Glycoxidation and Cross-Linking Diabetes, February 1, 2005; 54(2): 517 - 526. [Abstract] [Full Text] [PDF]