This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this book Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ulrich, P. Articles by Cerami, A. Search for Related Content PubMed PubMed Citation Articles by Ulrich, P. Articles by Cerami, A.

Protein Glycation, Diabetes, and Aging

The Kenneth S. Warren Laboratories, 765 Old Saw Mill River Road, Tarrytown, New York 10591

ABSTRACT

Biological amines react with reducing sugars to form a complex family of rearranged and dehydrated covalent adducts that are often yellow-brown and/or fluorescent and include many cross-linked structures. Food chemists have long studied this process as a source of flavor, color, and texture changes in cooked, processed, and stored foods. During the 1970s and 1980s, it was realized that this process, called the Maillard reaction or advanced glycation, also occurs slowly in vivo. Advanced glycation endproducts (AGEs) that form are implicated, causing the complications of diabetes and aging, primarily via adventitious and crosslinking of proteins. Long-lived proteins such as structural collagen and lens crystallins particularly are implicated as pathogenic targets of AGE processes. AGE formation in vascular wall collagen appears to be an especially deleterious event, causing crosslinking of collagen molecules to each other and to circulating proteins. This leads to plaque formation, basement membrane thickening, and loss of vascular elasticity. The chemistry of these later-stage, glycation-derived crosslinks is still incompletely understood but, based on the hypothesis that AGE formation involves reactive carbonyl groups, the authors introduced the carbonyl reagent ami- noguanidine hydrochloride as an inhibitor of AGE formation in vivo in the mid 1980s. Subsequent studies by many researchers have shown the effectiveness of aminoguanidine in slowing or preventing a wide range of complications of diabetes and aging in animals and, recently, in humans. Since, the authors have developed a new class of agents, exemplified by 4,5-dimethyl-3-phenacylthiazolium chloride (DPTC), which can chemically break already-formed AGE protein-protein crosslinks. These agents are based on a new theory of AGE crosslinking that postulates that -dicarbonyl structures are present in AGE protein-protein crosslinks. In studies in aged animals, DPTC has been shown to be capable of reverting indices of vascular compliance to levels seen in younger animals. Human clinical trials are underway.

This article has been cited by other articles:

				L. Shamir, C. A. Wolkow, and I. G. Goldberg Quantitative measurement of aging using image texture entropy Bioinformatics, December 1, 2009; 25(23): 3060 - 3063. [Abstract] [Full Text] [PDF]

				E. C. Tuday, D. Nyhan, A. A. Shoukas, and D. E. Berkowitz Simulated microgravity-induced aortic remodeling J Appl Physiol, June 1, 2009; 106(6): 2002 - 2008. [Abstract] [Full Text] [PDF]

				B. Bartling, M. Desole, S. Rohrbach, R.-E. Silber, and A. Simm Age-associated changes of extracellular matrix collagen impair lung cancer cell migration FASEB J, May 1, 2009; 23(5): 1510 - 1520. [Abstract] [Full Text] [PDF]

				J. Uribarri, A. Stirban, D. Sander, W. Cai, M. Negrean, C. E. Buenting, T. Koschinsky, and H. Vlassara Single Oral Challenge by Advanced Glycation End Products Acutely Impairs Endothelial Function in Diabetic and Nondiabetic Subjects Diabetes Care, October 1, 2007; 30(10): 2579 - 2582. [Abstract] [Full Text] [PDF]

				P. Newsholme, E. P. Haber, S. M. Hirabara, E. L. O. Rebelato, J. Procopio, D. Morgan, H. C. Oliveira-Emilio, A. R. Carpinelli, and R. Curi Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity J. Physiol., August 15, 2007; 583(1): 9 - 24. [Abstract] [Full Text] [PDF]

				T. Kueper, T. Grune, S. Prahl, H. Lenz, V. Welge, T. Biernoth, Y. Vogt, G.-M. Muhr, A. Gaemlich, T. Jung, et al. Vimentin Is the Specific Target in Skin Glycation: STRUCTURAL PREREQUISITES, FUNCTIONAL CONSEQUENCES, AND ROLE IN SKIN AGING J. Biol. Chem., August 10, 2007; 282(32): 23427 - 23436. [Abstract] [Full Text] [PDF]

				J. Uribarri, W. Cai, M. Peppa, S. Goodman, L. Ferrucci, G. Striker, and H. Vlassara Circulating Glycotoxins and Dietary Advanced Glycation Endproducts: Two Links to Inflammatory Response, Oxidative Stress, and Aging J. Gerontol. A Biol. Sci. Med. Sci., April 1, 2007; 62(4): 427 - 433. [Abstract] [Full Text] [PDF]

				S. A. C. Chong, W. Lee, P. D. Arora, C. Laschinger, E. W. K. Young, C. A. Simmons, M. Manolson, J. Sodek, and C. A. McCulloch Methylglyoxal Inhibits the Binding Step of Collagen Phagocytosis J. Biol. Chem., March 16, 2007; 282(11): 8510 - 8520. [Abstract] [Full Text] [PDF]

				A. M. Vincent, L. Perrone, K. A. Sullivan, C. Backus, A. M. Sastry, C. Lastoskie, and E. L. Feldman Receptor for Advanced Glycation End Products Activation Injures Primary Sensory Neurons via Oxidative Stress Endocrinology, February 1, 2007; 148(2): 548 - 558. [Abstract] [Full Text] [PDF]

				M. P. Fautsch, D. H. Johnson, and the Second ARVO/Pfizer Research Institute Working Aqueous humor outflow: what do we know? Where will it lead us? Invest. Ophthalmol. Vis. Sci., October 1, 2006; 47(10): 4181 - 4187. [Full Text] [PDF]

				J. Asbun and F. J. Villarreal The Pathogenesis of Myocardial Fibrosis in the Setting of Diabetic Cardiomyopathy J. Am. Coll. Cardiol., February 21, 2006; 47(4): 693 - 700. [Abstract] [Full Text] [PDF]

				G. T. Wondrak, M. K. Jacobson, and E. L. Jacobson Antimelanoma Activity of Apoptogenic Carbonyl Scavengers J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 805 - 814. [Abstract] [Full Text] [PDF]

				G Hein, C Weiss, G Lehmann, T Niwa, G Stein, and S Franke Advanced glycation end product modification of bone proteins and bone remodelling: hypothesis and preliminary immunohistochemical findings Ann Rheum Dis, January 1, 2006; 65(1): 101 - 104. [Abstract] [Full Text] [PDF]

				C. Iacobini, G. Oddi, S. Menini, L. Amadio, C. Ricci, C. Di Pippo, M. Sorcini, F. Pricci, F. Pugliese, and G. Pugliese Development of age-dependent glomerular lesions in galectin-3/AGE-receptor-3 knockout mice Am J Physiol Renal Physiol, September 1, 2005; 289(3): F611 - F621. [Abstract] [Full Text] [PDF]

				R. Ramasamy, S. J. Vannucci, S. S. D. Yan, K. Herold, S. F. Yan, and A. M. Schmidt Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation Glycobiology, July 1, 2005; 15(7): 16R - 28R. [Abstract] [Full Text] [PDF]

				H. H. Dao, R. Essalihi, C. Bouvet, and P. Moreau Evolution and modulation of age-related medial elastocalcinosis: Impact on large artery stiffness and isolated systolic hypertension Cardiovasc Res, May 1, 2005; 66(2): 307 - 317. [Abstract] [Full Text] [PDF]

				M. Diamant, H. J. Lamb, M. A. van de Ree, E. L. Endert, Y. Groeneveld, M. L. Bots, P. J. Kostense, and J. K. Radder The Association between Abdominal Visceral Fat and Carotid Stiffness Is Mediated by Circulating Inflammatory Markers in Uncomplicated Type 2 Diabetes J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1495 - 1501. [Abstract] [Full Text] [PDF]

				S.-i. Akazawa, T. Karino, N. Yoshida, T. Katsuragi, and Y. Tani Functional Analysis of Fructosyl-Amino Acid Oxidases of Aspergillus oryzae Appl. Envir. Microbiol., October 1, 2004; 70(10): 5882 - 5890. [Abstract] [Full Text] [PDF]

				H. Konishi, M. Nakatsuka, C. Chekir, S. Noguchi, Y. Kamada, A. Sasaki, and Y. Hiramatsu Advanced glycation end products induce secretion of chemokines and apoptosis in human first trimester trophoblasts Hum. Reprod., September 1, 2004; 19(9): 2156 - 2162. [Abstract] [Full Text] [PDF]

				L Kessel, B Sander, P Dalgaard, and M Larsen Lens fluorescence and metabolic control in type 1 diabetic patients: a 14 year follow up study Br J Ophthalmol, September 1, 2004; 88(9): 1169 - 1172. [Abstract] [Full Text] [PDF]

				J.-L. Wautier and A. M. Schmidt Protein Glycation: A Firm Link to Endothelial Cell Dysfunction Circ. Res., August 6, 2004; 95(3): 233 - 238. [Abstract] [Full Text] [PDF]

				R. P. Wildman, L. L. Schott, S. Brockwell, L. H. Kuller, and K. Sutton-Tyrrell A dietary and exercise intervention slows menopause-associated progression of subclinical atherosclerosis as measured by intima-media thickness of the carotid arteries J. Am. Coll. Cardiol., August 4, 2004; 44(3): 579 - 585. [Abstract] [Full Text] [PDF]

				Y.-G. Choi, J.-I. Kim, Y.-C. Jeon, S.-J. Park, E.-K. Choi, R. Rubenstein, R. J. Kascsak, R. I. Carp, and Y.-S. Kim Nonenzymatic Glycation at the N Terminus of Pathogenic Prion Protein in Transmissible Spongiform Encephalopathies J. Biol. Chem., July 16, 2004; 279(29): 30402 - 30409. [Abstract] [Full Text] [PDF]

				J. V. Valencia, M. Mone, J. Zhang, M. Weetall, F. P. Buxton, and T. E. Hughes Divergent Pathways of Gene Expression Are Activated by the RAGE Ligands S100b and AGE-BSA Diabetes, March 1, 2004; 53(3): 743 - 751. [Abstract] [Full Text] [PDF]

				T. O. Metz, N. L. Alderson, M. E. Chachich, S. R. Thorpe, and J. W. Baynes Pyridoxamine Traps Intermediates in Lipid Peroxidation Reactions in Vivo: EVIDENCE ON THE ROLE OF LIPIDS IN CHEMICAL MODIFICATION OF PROTEIN AND DEVELOPMENT OF DIABETIC COMPLICATIONS J. Biol. Chem., October 24, 2003; 278(43): 42012 - 42019. [Abstract] [Full Text] [PDF]

				R. P. Wildman, R. H. Mackey, A. Bostom, T. Thompson, and K. Sutton-Tyrrell Measures of Obesity Are Associated With Vascular Stiffness in Young and Older Adults Hypertension, October 1, 2003; 42(4): 468 - 473. [Abstract] [Full Text] [PDF]

				E. A. McRobert, M. Gallicchio, G. Jerums, M. E. Cooper, and L. A. Bach The Amino-terminal Domains of the Ezrin, Radixin, and Moesin (ERM) Proteins Bind Advanced Glycation End Products, an Interaction That May Play a Role in the Development of Diabetic Complications J. Biol. Chem., July 3, 2003; 278(28): 25783 - 25789. [Abstract] [Full Text] [PDF]

				K. R. Bidasee, K. Nallani, Y. Yu, R. R. Cocklin, Y. Zhang, M. Wang, U. D. Dincer, and H. R. Besch Jr. Chronic Diabetes Increases Advanced Glycation End Products on Cardiac Ryanodine Receptors/Calcium-Release Channels Diabetes, July 1, 2003; 52(7): 1825 - 1836. [Abstract] [Full Text] [PDF]

				R. M.A. Henry, P. J. Kostense, A. M.W. Spijkerman, J. M. Dekker, G. Nijpels, R. J. Heine, O. Kamp, N. Westerhof, L. M. Bouter, and C. D.A. Stehouwer Arterial Stiffness Increases With Deteriorating Glucose Tolerance Status: The Hoorn Study Circulation, April 29, 2003; 107(16): 2089 - 2095. [Abstract] [Full Text] [PDF]

				D. A. Kass Getting Better Without AGE: New Insights Into the Diabetic Heart Circ. Res., April 18, 2003; 92(7): 704 - 706. [Full Text] [PDF]

				K. L. Herrmann, A. D. McCulloch, and J. H. Omens Glycated collagen cross-linking alters cardiac mechanics in volume-overload hypertrophy Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1277 - H1284. [Abstract] [Full Text] [PDF]

				K. Cruickshank, L. Riste, S. G. Anderson, J. S. Wright, G. Dunn, and R. G. Gosling Aortic Pulse-Wave Velocity and Its Relationship to Mortality in Diabetes and Glucose Intolerance: An Integrated Index of Vascular Function? Circulation, October 15, 2002; 106(16): 2085 - 2090. [Abstract] [Full Text] [PDF]

				M. Portero-Otin, R. Pamplona, M. J. Bellmunt, M. C. Ruiz, J. Prat, R. Salvayre, and A. Negre-Salvayre Advanced Glycation End Product Precursors Impair Epidermal Growth Factor Receptor Signaling Diabetes, May 1, 2002; 51(5): 1535 - 1542. [Abstract] [Full Text] [PDF]