Advanced glycation end products, diabetes and ageing

Fortgeschrittene Glykierungsendprodukte, Diabetes und Altern

Abstract

Advanced glycation end products (AGEs) are formed in vivo by a non-enzymatic reaction of proteins with carbohydrates and accumulate in many tissues during ageing. They are discussed as being responsible for many age- and diabetes-related diseases. On the other hand, AGEs are formed by the heating of food and are taken up by the nutrition. The contribution of endogenously formed versus exogenous intake of AGEs to age-related diseases is still under discussion.

Zusammenfassung

Fortgeschrittene Glykierungsendprodukte (AGEs) werden in vivo durch eine nicht-enzymatische chemische Reaktion von Proteinen mit Kohlenhydraten gebildet und reichern sich in vielen Geweben mit dem Alter an. Sie werden für die Auslösung von alters- und Diabetes-induzierten Erkrankungen mitverantwortlich gemacht. Andererseits entstehen AGEs durch die Erhitzung von Lebensmitteln, die mit der Nahrung aufgenommen werden. Inwieweit nun endogene oder exogen-aufgenommene AGEs die größere Rolle bei der Entstehung von degenerativen Erkrankungen ist noch nicht geklärt.

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References

  1. 1.

    Oeppen J, Vaupel JW (2002) Demography. Broken limits to life expectancy. Science 296:1029–1031

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Olshansky SJ, Passaro DJ, Hershow RC, Layden J, Carnes BA, Brody J, Hayflick L, Butler RN, Allison DB, Ludwig DS (2005) A potential decline in life expectancy in the United States in the 21st century. N Engl J Med 352:1138–1145

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Daniels SR (2006) The consequences of childhood overweight and obesity. Future Child 16:47–67

    PubMed  Article  Google Scholar 

  4. 4.

    Bunn HF, Higgins PJ (1981) Reaction of monosaccharides with proteins: possible evolutionary significance. Science 213:222–224

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Lo TW, Westwood ME, McLellan AC, Selwood T, Thornalley PJ (1994) Binding and modification of proteins by methylglyoxal under physiological conditions. A kinetic and mechanistic study with N alpha-acetylarginine, N alpha-acetylcysteine, and N alphaacetyllysine, and bovine serum albumin. J Biol Chem 269:32299–32305

    PubMed  CAS  Google Scholar 

  6. 6.

    Ferreira AE, Ponces Freire AM, Voit EO (2003) A quantitative model of the generation of N(epsilon)-(carboxymethyl) lysine in the Maillard reaction between collagen and glucose. Biochem J 376:109–121

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Glomb MA, Monnier VM (1995) Mechanism of protein modification by glyoxal and glycolaldehyde, reactive intermediates of the Maillard reaction. J Biol Chem 270:10017–10026

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Namiki M (2003) Advances in the Maillard reaction and glycation researches – mainly on the Namiki pathway. Seikagaku 75:37–42

    PubMed  CAS  Google Scholar 

  9. 9.

    Sato T, Iwaki M, Shimogaito N, Wu X, Yamagishi S, Takeuchi M (2006) TAGE (toxic AGEs) theory in diabetic complications. Curr Mol Med 6:351–358

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Sato T, Shimogaito N, Wu X, Kikuchi S, Yamagishi S, Takeuchi M (2006) Toxic advanced glycation end products (TAGE) theory in Alzheimer's disease. Am J Alzheimers Dis Other Demen 21:197–208

    PubMed  Article  Google Scholar 

  11. 11.

    Koschinsky T, He CJ, Mitsuhashi T, Bucala R, Liu C, Buenting C, Heitmann K, Vlassara H (1997) Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor in diabetic nephropathy. Proc Natl Acad Sci USA 94:6474–6479

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Somoza V (2007) The maillard reaction in food and medicine. Mol Nutr Food Res 51:381–382

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Ahmed N, Thornalley PJ (2005) Peptide mapping of human serum albumin modified minimally by methylglyoxal in vitro and in vivo. Ann NY Acad Sci 1043:260–266

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Zeng J, Davies MJ (2005) Evidence for the formation of adducts and S-(carboxymethyl)cysteine on reaction of alpha-dicarbonyl compounds with thiol groups on amino acids, peptides, and proteins. Chem Res Toxicol 18:1232–1241

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Friguet B, Stadtman ER, Szweda LI (1994) Modification of glucose-6-phosphate dehydrogenase by 4-hydroxy-2-nonenal. Formation of crosslinked protein that inhibits the multicatalytic protease. J Biol Chem 269:21639–21643

    PubMed  CAS  Google Scholar 

  16. 16.

    Bulteau AL, Verbeke P, Petropoulos I, Chaffotte AF, Friguet B (2001) Proteasome inhibition in glyoxal-treated fibroblasts and resistance of glycated glucose-6-phosphate dehydrogenase to 20 S proteasome degradation in vitro. J Biol Chem 276:45662–45668

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Badenhorst D, Maseko M, Tsotetsi OJ, Naidoo A, Brooksbank R, Norton GR, Woodiwiss AJ (2003) Cross-linking influences the impact of quantitative changes in myocardial collagen on cardiac stiffness and remodelling in hypertension in rats. Cardiovasc Res 57:632–641

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Yao D, Taguchi T, Matsumura T, Pestell R, Edelstein D, Giardino I, Suske G, Ahmed N, Thornalley PJ, Sarthy VP et al (2006) Methylglyoxal modification of mSin3A links glycolysis to angiopoietin-2 transcription. Cell 124:275–286

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Hernebring M, Brolen G, Aguilaniu H, Semb H, Nystrom T (2006) Elimination of damaged proteins during differentiation of embryonic stem cells. Proc Natl Acad Sci USA 103:7700–7705

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Bierhaus A, Humpert PM, Morcos M, Wendt T, Chavakis T, Arnold B, Stern DM, Nawroth PP (2005) Understanding RAGE, the receptor for advanced glycation end products. J Mol Med 83:876–886

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Westwood ME, McLellan AC, Thornalley PJ (1994) Receptor-mediated endocytic uptake of methylglyoxal-modified serum albumin. Competition with advanced glycation end product-modified serum albumin at the advanced glycation end product receptor. J Biol Chem 269:32293–32298

    PubMed  CAS  Google Scholar 

  22. 22.

    Kuniyasu A, Ohgami N, Hayashi S, Miyazaki A, Horiuchi S, Nakayama H (2003) CD36-mediated endocytic uptake of advanced glycation end products (AGE) in mouse 3T3-L1 and human subcutaneous adipocytes. FEBS Lett 537:85–90

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Li YM, Mitsuhashi T, Wojciechowicz D, Shimizu N, Li J, Stitt A, He C, Banerjee D, Vlassara H (1996) Molecular identity and cellular distribution of advanced glycation endproduct receptors: relationship of p60 to OST-48 and p90 to 80K-H membrane proteins. Proc Natl Acad Sci USA 93:11047–11052

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Hodgkinson CP, Mander A, Sale GJ (2005) Identification of 80K-H as a protein involved in GLUT4 vesicle trafficking. Biochem J 388:785–793

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Fukushi J, Makagiansar IT, Stallcup WB (2004) NG2 proteoglycan promotes endothelial cell motility and angiogenesis via engagement of galectin-3 and alpha3beta1 integrin. Mol Biol Cell 15:3580–3590

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Gaudin JC, Mehul B, Hughes RC (2000) Nuclear localisation of wild type and mutant galectin-3 in transfected cells. Biol Cell 92:49–58

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Iacobini C, Amadio L, Oddi G, Ricci C, Barsotti P, Missori S, Sorcini M, Di Mario U, Pricci F, Pugliese G (2003) Role of galectin-3 in diabetic nephropathy. J Am Soc Nephrol 14: S264–270

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Schleicher ED, Wagner E, Nerlich AG (1997) Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging. J Clin Invest 99:457–468

    PubMed  CAS  Google Scholar 

  29. 29.

    Simm A, Wagner J, Gursinsky T, Nass N, Friedrich I, Schinzel R, Czeslik E, Silber RE, Scheubel RJ (2007) Advanced glycation endproducts: a biomarker for age as an outcome predictor after cardiac surgery? Exp Gerontol 42:668–675

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Dyer DG, Dunn JA, Thorpe SR, Lyons TJ, McCance DR, Baynes JW (1992) Accumulation of Maillard reaction products in skin collagen in diabetes and aging. Ann NY Acad Sci 663:421–422

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Verzijl N, DeGroot J, Oldehinkel E, Bank RA, Thorpe SR, Baynes JW, Bayliss MT, Bijlsma JW, Lafeber FP, Tekoppele JM (2000) Age-related accumulation of Maillard reaction products in human articular cartilage collagen. Biochem J 350 Pt 2:381–387

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Sato Y, Kondo T, Ohshima T (2001) Estimation of age of human cadavers by immunohistochemical assessment of advanced glycation end products in the hippocampus. Histopathology 38:217–220

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Sell DR, Kleinman NR, Monnier VM (2000) Longitudinal determination of skin collagen glycation and glycoxidation rates predicts early death in C57BL/6NNIA mice. Faseb J 14:145–156

    PubMed  CAS  Google Scholar 

  34. 34.

    Sebekova K, Hofmann T, Boor P, Sebekova K Jr, Ulicna O, Erbersdobler HF, Baynes JW, Thorpe SR, Heidland A, Somoza V (2005) Renal effects of oral maillard reaction product load in the form of bread crusts in healthy and subtotally nephrectomized rats. Ann NY Acad Sci 1043:482–491

    PubMed  Article  CAS  Google Scholar 

  35. 35.

    Stitt AW, Curtis TM (2005) Advanced glycation and retinal pathology during diabetes. Pharmacol Rep 57 (Suppl):156–168

    PubMed  Google Scholar 

  36. 36.

    Brownlee M, Vlassara H, Cerami A (1985) Nonenzymatic glycosylation products on collagen covalently trap low-density lipoprotein. Diabetes 34:938–941

    PubMed  Article  CAS  Google Scholar 

  37. 37.

    Park L, Raman KG, Lee KJ, Lu Y, Ferran LJ Jr, Chow WS, Stern D, Schmidt AM (1998) Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts. Nat Med 4:1025–1031

    PubMed  Article  CAS  Google Scholar 

  38. 38.

    Vlassara H, Fuh H, Donnelly T, Cybulsky M (1995) Advanced glycation endproducts promote adhesion molecule (VCAM-1, ICAM-1) expression and atheroma formation in normal rabbits. Mol Med 1:447–456

    PubMed  CAS  Google Scholar 

  39. 39.

    Koyama H, Shoji T, Yokoyama H, Motoyama K, Mori K, Fukumoto S, Emoto M, Tamei H, Matsuki H, Sakurai S et al (2005) Plasma level of endogenous secretory RAGE is associated with components of the metabolic syndrome and atherosclerosis. Arterioscler Thromb Vasc Biol 25:2587–2593

    PubMed  Article  CAS  Google Scholar 

  40. 40.

    Koyama H, Shoji T, Fukumoto S, Shinohara K, Emoto M, Mori K, Tahara H, Ishimura E, Kakiya R, Tabata T et al (2006) Low circulating endogenous secretory receptor for AGEs predicts cardiovascular mortality in patients with end-stage renal disease. Arterioscler Thromb Vasc Biol 27:147–153

    PubMed  Article  CAS  Google Scholar 

  41. 41.

    Wautier JL, Zoukourian C, Chappey O, Wautier MP, Guillausseau PJ, Cao R, Hori O, Stern D, Schmidt AM (1996) Receptor-mediated endothelial cell dysfunction in diabetic vasculopathy. Soluble receptor for advanced glycation end products blocks hyperpermeability in diabetic rats. J Clin Invest 97:238–243

    PubMed  CAS  Google Scholar 

  42. 42.

    Schmidt AM, Hori O, Chen JX, Li JF, Crandall J, Zhang J, Cao R, Yan SD, Brett J, Stern D (1995) Advanced glycation endproducts interacting with their endothelial receptor induce expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells and in mice. A potential mechanism for the accelerated vasculopathy of diabetes. J Clin Invest 96:1395–1403

    PubMed  CAS  Google Scholar 

  43. 43.

    Wang AL, Yu AC, He QH, Zhu X, Tso MO (2007) AGEs mediated expression and secretion of TNF alpha in rat retinal microglia. Exp Eye Res 84:905–913

    PubMed  Article  CAS  Google Scholar 

  44. 44.

    Shanmugam N, Kim YS, Lanting L, Natarajan R (2003) Regulation of cyclooxygenase-2 expression in monocytes by ligation of the receptor for advanced glycation end products. J Biol Chem 278:34834–34844

    PubMed  Article  CAS  Google Scholar 

  45. 45.

    Veiga da-Cunha M, Jacquemin P, Delpierre G, Godfraind C, Theate I, Vertommen D, Clotman F, Lemaigre F, Devuyst O, Van Schaftingen E (2006) Increased protein glycation in fructosamine 3-kinase-deficient mice. Biochem J 399:257–264

    PubMed  Article  CAS  Google Scholar 

  46. 46.

    Thornalley PJ (1998) Glutathione-dependent detoxification of alpha-oxoaldehydes by the glyoxalase system: involvement in disease mechanisms and antiproliferative activity of glyoxalase I inhibitors. Chem Biol Interact 111–112:137–151

    PubMed  Article  Google Scholar 

  47. 47.

    Thornalley PJ (1995) Advances in glyoxalase research. Glyoxalase expression in malignancy, anti-proliferative effects of methylglyoxal, glyoxalase I inhibitor diesters and SD-lactoylglutathione, and methylglyoxal-modified protein binding and endocytosis by the advanced glycation endproduct receptor. Crit Rev Oncol Hematol 20:99–128

    PubMed  Article  CAS  Google Scholar 

  48. 48.

    Levi B, Werman MJ (1998) Long-term fructose consumption accelerates glycation and several age-related variables in male rats. J Nutr 128:1442–1449

    PubMed  CAS  Google Scholar 

  49. 49.

    Gaby AR (2005) Adverse effects of dietary fructose. Altern Med Rev 10:294–306

    PubMed  Google Scholar 

  50. 50.

    Somoza V (2005) Five years of research on health risks and benefits of Maillard reaction products: an update. Mol Nutr Food Res 49:663–672

    PubMed  Article  CAS  Google Scholar 

  51. 51.

    Somoza V, Wenzel E, Weiss C, Clawin-Radecker I, Grubel N, Erbersdobler HF (2006) Dose-dependent utilisation of casein-linked lysinoalanine, N(epsilon)-fructoselysine and N (epsilon)-carboxymethyllysine in rats. Mol Nutr Food Res 50:833–841

    PubMed  Article  CAS  Google Scholar 

  52. 52.

    Ames JM, Wynne A, Hofmann A, Plos S, Gibson GR (1999) The effect of a model melanoidin mixture on faecal bacterial populations in vitro. Br J Nutr 82:489–495

    PubMed  CAS  Google Scholar 

  53. 53.

    Grunwald S, Krause R, Bruch M, Henle T, Brandsch M (2006) Transepithelial flux of early and advanced glycation compounds across Caco-2 cell monolayers and their interaction with intestinal amino acid and peptide transport systems. Br J Nutr 95:1221–1228

    PubMed  Article  CAS  Google Scholar 

  54. 54.

    Li SY, Liu Y, Sigmon VK, McCort A, Ren J (2005) High-fat diet enhances visceral advanced glycation end products, nuclear O-Glc-Nac modification, p38 mitogen-activated protein kinase activation and apoptosis. Diabetes Obes Metab 7:448–454

    PubMed  Article  CAS  Google Scholar 

  55. 55.

    Hofmann MA, Lalla E, Lu Y, Gleason MR, Wolf BM, Tanji N, Ferran LJ Jr, Kohl B, Rao V, Kisiel W et al (2001) Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model. J Clin Invest 107:675–683

    PubMed  CAS  Article  Google Scholar 

  56. 56.

    Faist V, Lindenmeier M, Geisler C, Erbersdobler HF, Hofmann T (2002) Influence of molecular weight fractions isolated from roasted malt on the enzyme activities of NADPH-cytochrome c-reductase and glutathione-S-transferase in Caco-2 cells. J Agric Food Chem 50:602–606

    PubMed  Article  CAS  Google Scholar 

  57. 57.

    Esposito C, Fasoli G, Plati AR, Bellotti N, Conte MM, Cornacchia F, Foschi A, Mazzullo T, Semeraro L, Dal Canton A (2001) Long-term exposure to high glucose up-regulates VCAM-induced endothelial cell adhesiveness to PBMC. Kidney Int 59:1842–1849

    PubMed  Article  CAS  Google Scholar 

  58. 58.

    Zill H, Bek S, Hofmann T, Huber J, Frank O, Lindenmeier M,Weigle B, Erbersdobler HF, Scheidler S, Busch AE et al (2003) RAGE-mediated MAPK activation by food-derived AGE and non-AGE products. Biochem Biophys Res Commun 300:311–315

    PubMed  Article  CAS  Google Scholar 

  59. 59.

    Zill H, Gunther R, Erbersdobler HF, Folsch UR, Faist V (2001) RAGE expression and AGE-induced MAP kinase activation in Caco-2 cells. Biochem Biophys Res Commun 288:1108–1111

    PubMed  Article  CAS  Google Scholar 

  60. 60.

    Mizutani K, Ikeda K, Kawai Y, Yamori Y (1998) Resveratrol stimulates the proliferation and differentiation of osteoblastic MC3T3-E1 cells. Biochem Biophys Res Commun 253:859–863

    PubMed  Article  CAS  Google Scholar 

  61. 61.

    Mizutani K, Ikeda K, Nishikata T, Yamori Y (2000) Phytoestrogens attenuate oxidative DNA damage in vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats. J Hypertens 18:1833–1840

    PubMed  Article  CAS  Google Scholar 

  62. 62.

    Reddy VP, Beyaz A (2006) Inhibitors of the Maillard reaction and AGE breakers as therapeutics for multiple diseases. Drug Discov Today 11:646–654

    PubMed  Article  CAS  Google Scholar 

  63. 63.

    Stadler K, Jenei V, Somogyi A, Jakus J (2005) Beneficial effects of aminoguanidine on the cardiovascular system of diabetic rats. Diabetes Metab Res Rev 21:189–196

    PubMed  Article  CAS  Google Scholar 

  64. 64.

    Bolton WK, Cattran DC, Williams ME, Adler SG, Appel GB, Cartwright K, Foiles PG, Freedman BI, Raskin P, Ratner RE et al (2004) Randomized trial of an inhibitor of formation of advanced glycation end products in diabetic nephropathy. Am J Nephrol 24:32–40

    PubMed  Article  CAS  Google Scholar 

  65. 65.

    Asif M, Egan J, Vasan S, Jyothirmayi GN, Masurekar MR, Lopez S, Williams C, Torres RL, Wagle D, Ulrich P et al (2000) An advanced glycation endproduct cross-link breaker can reverse age-related increases in myocardial stiffness. Proc Natl Acad Sci USA 97:2809–2813

    PubMed  Article  CAS  Google Scholar 

  66. 66.

    Wolffenbuttel BH, Boulanger CM, Crijns FR, Huijberts MS, Poitevin P, Swennen GN, Vasan S, Egan JJ, Ulrich P, Cerami A et al (1998) Breakers of advanced glycation end products restore large artery properties in experimental diabetes. Proc Natl Acad Sci USA 95:4630–4634

    PubMed  Article  CAS  Google Scholar 

  67. 67.

    Little WC, Zile MR, Kitzman DW, Hundley WG, O'Brien TX, Degroof RC (2005) The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure. J Card Fail 11:191–195

    PubMed  Article  CAS  Google Scholar 

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Correspondence to A. Simm.

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Nass, N., Bartling, B., Navarrete Santos, A. et al. Advanced glycation end products, diabetes and ageing. Z Gerontol Geriat 40, 349–356 (2007). https://doi.org/10.1007/s00391-007-0484-9

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Key words

  • advanced glycation endproducts
  • degenerative diseases
  • cell signalling

Schlüsselwörter

  • Glykierungsendprodukte
  • Degenerative Erkrankungen
  • Signaltransduktion