Vnitr Lek 2014, 60(9):720-724

AGEs and RAGE - advanced glycation end-products and their receptor in questions and answers

Marta Kalousová, Tomáš Zima*
Ústav lékařské biochemie a laboratorní diagnostiky 1. LF UK a VFN Praha, přednosta prof. MUDr. Tomáš Zima, DrSc., MBA

Advanced glycation end products (AGEs) play an important role in the pathogenesis of chronic diseases and their complications, especially diabetic complications, atherosclerosis, complications of chronic kidney diseases and neurodegenerative diseases. These substances are formed via non-enzymatic glycation and their formation is potentiated in case of carbonyl stress. AGEs are represented by a heterogeneous group of compounds, e.g. carboxymethyllysine, pentosine, methylglyoxallysin dimer, vesperlysine, imidazolones etc. AGEs can modify proteins and so change their physical and chemical properties and can act also via specific receptors, among them RAGE (receptor for advanced glycation end products) is the best known but not the unique one. RAGE is a multiligand receptor capable to bind also HMGB1 (high mobility group box protein 1), S100 proteins or amyloid fibrils. RAGE - ligand interactions results to activation of a variety of signaling pathways including oxidative stress and activation of nuclear factor κB and subsequent proinflammatory response depending on the cell type. AGEs and RAGE together with further mechanisms - hexosamine pathway, polyol pathway, lipid metabolism disorder, activation of proteinkinase C, oxidative stress and inflammatory reaction take part in the pathogenesis of diabetic complications. Terapeuticaly it is possible to decrease endogenous formation of AGEs, influence the AGEs intake to the organism and their absorption in the intestine or stimulate their degradation.

Keywords: AGEs; advanced glycation end-products; carbonyl stress; diabetes mellitus; inflammation; oxidative stress; RAGE; receptor for AGEs; sRAGE

Received: June 26, 2014; Accepted: July 17, 2014; Published: September 1, 2014  Show citation

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Kalousová M, Zima T. AGEs and RAGE - advanced glycation end-products and their receptor in questions and answers. Vnitr Lek. 2014;60(9):720-724.
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    References

    1. Maillard LC. Action des acides amines sur les sucres; formacion des melaniodines par voie methodique. CR Acad Sci 1912; 154: 66-68.
    2. Garlick RL, Mazer JS, Chylack jr. LT et al. Nonenzymatic glycation of human lens crystallin. Effect of aging and diabetes mellitus. J Clin Invest 1984; 74(5): 1742-1749. Go to original source... Go to PubMed...
    3. Brownlee M, Vlassara H, Cerami A. Nonenzymatic glycosylation and the pathogenesis of diabetic complications. Ann Intern Med 1984; 101(4): 527-537. Go to original source... Go to PubMed...
    4. Vishwanath V, Frank KE, Elmets CA et al. Glycation of skin collagen in type I diabetes mellitus. Correlation with long-term complications. Diabetes 1986; 35(8): 916-921. Go to original source... Go to PubMed...
    5. Makita Z, Radoff S, Rayfield EJ et al. Advanced glycosylation end products in patients with diabetic nephropathy. N Engl J Med 1991; 325(12): 836-842. Go to original source... Go to PubMed...
    6. Ritz E, Deppisch R, Nawroth P. Toxicity of uremia - does it come from AGE? Nephrol Dial Transplant 1994; 9(1): 1-2. Go to original source...
    7. Vlassara H. Serum advanced glycosylation end products: a new class of uremic toxins? Blood Purif 1994; 12(1): 54-59. Go to original source... Go to PubMed...
    8. Vitek MP, Bhattacharya K, Glendening JM et al. Advanced glycation end products contribute to amyloidosis in Alzheimer disease. Proc Natl Acad Sci USA 1994; 91(11): 4766-4770. Go to original source... Go to PubMed...
    9. Neeper M, Schmidt AM, Brett J et al. Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem 1992; 267(21): 14998-15004. Go to original source...
    10. Sparvero LJ, Asafu-Adjei D, Kang R et al. RAGE (Receptor for Advanced Glycation Endproducts), RAGE ligands, and their role in cancer and inflammation. J Transl Med 2009; 7: 17. Dostupné z DOI: <http://doi:10.1186/1479-5876-7-17>. Go to original source... Go to PubMed...
    11. Krechler T, Jáchymová M, Mestek O et al. Soluble receptor for advanced glycation end-products (sRAGE) and polymorphisms of RAGE and glyoxalase I genes in patients with pancreas cancer. Clin Biochem 2010; 43(10-11): 882-886. Go to original source... Go to PubMed...
    12. Miyata T, van Ypersele de Strihou C, Kurokawa K et al. Alterations in nonenzymatic biochemistry in uremia: Origin and significance of "carbonyl stress" in long-term uremic complications. Kidney Int 1999; 55(2): 389-399. Go to original source... Go to PubMed...
    13. Koenig RJ, Blobstein SH, Cerami A. Structure of carbohydrate of hemoglobin AIc. J Biol Chem 1977; 252(9): 2992-2997. Go to original source... Go to PubMed...
    14. Ames JM. Evidence against dietary advanced glycation endproducts being a risk to human health. Mol Nutr Food Res 2007; 51(9): 1085-1090. Go to original source... Go to PubMed...
    15. Sebeková K, Somoza V. Dietary advanced glycation endproducts (AGEs) and their health effects - PRO. Mol Nutr Food Res 2007; 51(9): 1079-1084. Go to original source... Go to PubMed...
    16. Koschinski T, He CJ, Mitsuhashi T et al. Orally absorbed reactive glycation products (glycotoxins): an enviromantal risk factor in diabetic nephropathy. Proc Natl Acad Sci USA 1997; 94(12): 6474-6479. Go to original source... Go to PubMed...
    17. Vlassara H, Cai W, Crandall J et al. Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy. Proc Natl Acad Sci USA 2002; 99(24): 15596-15601. Erratum in: Proc Natl Acad Sci USA 2003; 100(2): 763. Go to original source... Go to PubMed...
    18. Faist V, Ebersdobler HF. Metabolic transit and in vivo effects of melanoidins and precursor compounds deriving from the Maillard reaction. Ann Nutr Metab 2001; 45(1): 1-12. Go to original source... Go to PubMed...
    19. Hofmann MA, Drury S, Fu C et al. RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 1999; 97(7): 889-901. Go to original source... Go to PubMed...
    20. Hori O, Brett J, Slattery T et al. The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system. J Biol Chem 1995; 270(43): 25752-25761. Go to original source... Go to PubMed...
    21. Yan SD, Chen X, Fu J et al. RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. Nature 1996; 382 (6593): 685-691. Go to original source... Go to PubMed...
    22. Hitomi J, Yamaguchi K, Kikuchi Y et al. A novel calcium-binding protein in amniotic fluid, CAAF1: its molecular cloning and tissue distribution. J Cell Sci 1996; 109(Pt 4): 805-815. Go to original source... Go to PubMed...
    23. Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 2007; 81(1): 1-5. Go to original source... Go to PubMed...
    24. Pietzsch J, Hoppmann S. Human S100A12: a novel key player in inflammation? Amino Acids 2009; 36(3): 381-389. Go to original source... Go to PubMed...
    25. Sims GP, Rowe DC, Rietdijk ST et al. HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol 2010; 28: 367-388. Go to original source... Go to PubMed...
    26. Hodgkinson CP, Laxton RC, Patel K et al. Advanced glycation end-product of low density lipoprotein activates the toll-like 4 receptor pathway implications for diabetic atherosclerosis. Arterioscler Thromb Vasc Biol 2008; 28(12): 2275-2281. Go to original source... Go to PubMed...
    27. Vlassara H. The AGE-receptor in the pathogenesis of diabetic complications. Diabetes Metab Res Rev 2001; 17(6): 436-443. Go to original source... Go to PubMed...
    28. Park JS, Gamboni-Robertson F, He Q et al. High mobility group box 1 protein interacts with multiple Toll-like receptors. Am J Physiol Cell Physiol 2006; 290(3): C917-C924. Go to original source... Go to PubMed...
    29. Liliensiek B, Weigand MA, Bierhaus A et al. Receptor for advanced glycation end products (RAGE) regulates sepsis but not the adaptive immune response. J Clin Invest 2004; 113(11): 1641-1650. Go to original source... Go to PubMed...
    30. Yamamoto Y, Kato I, Doi T et al. Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice. J Clin Invest 2001; 108(2): 261-268. Go to original source... Go to PubMed...
    31. Hudson BI, Stickland MH, Futers TS et al. Effects of novel polymorphisms in the RAGE gene on transcriptional regulation and their association with diabetic retinopathy. Diabetes 2001; 50(6): 1505-1511. Go to original source... Go to PubMed...
    32. Kanková K, Stejskalová A, Hertlová M et al. Haplotype analysis of the RAGE gene: identification of a haplotype marker for diabetic nephropathy in type 2 diabetes mellitus. Nephrol Dial Transplant 2005; 20(6): 1093-1102. Go to original source... Go to PubMed...
    33. Hudson BI, Carter AM, Harja E et al. Identification, classification, and expression of RAGE gene splice variants. FASEB J 2008; 22(5): 1572-1580. Go to original source... Go to PubMed...
    34. Zhang L, Bukulin M, Kojro E et al. Receptor for advanced glycation end products is subjected to protein ectodomain shedding by metalloproteinases. J Biol Chem 2008; 283 (51): 35507-35516. Go to original source... Go to PubMed...
    35. Park SJ, Kleffmann T, Hessian PA. The G82S polymorphism promotes glycosylation of the receptor for advanced glycation end products (RAGE) at asparagine 81: comparison of wild-type rage with the G82S polymorphic variant. J Biol Chem 2011; 286(24): 21384-21392. Go to original source... Go to PubMed...
    36. Osawa M, Yamamoto Y, Munesue S et al. De-N-glycosylation or G82S mutation of RAGE sensitizes its interaction with advanced glycation endproducts. Biochim Biophys Acta 2007; 1770(10): 1468-1474. Go to original source... Go to PubMed...
    37. Kalousová M, Jáchymová M, Mestek O et al. Receptor for advanced glycation end products - soluble form and gene polymorphisms in chronic haemodialysis patients. Nephrol Dial Transplant 2007; 22(7): 2020-2026. Go to original source... Go to PubMed...
    38. Jang Y, Kim JY, Kang SM et al. Association of the Gly82Ser polymorphism in the receptor for advanced glycation end products (RAGE) gene with circulating levels of soluble RAGE and inflammatory markers in nondiabetic and nonobese Koreans. Metabolism 2007; 56(2): 199-205. Go to original source... Go to PubMed...
    39. Kalousová M, Jáchymová M, Germanová A et al. Genetic predisposition to advanced glycation end products toxicity is related to prognosis of chronic hemodialysis patients. Kidney Blood Press Res 2010; 33(1): 30-36. Go to original source... Go to PubMed...
    40. Barua M, Jenkins EC, Chen W et al. Glyoxalase I polymorphism rs2736654 causing the Ala111Glu substitution modulates enzyme activity - implications for autism. Autism Res 2011; 4(4): 262-270. Go to original source... Go to PubMed...
    41. Kalousová M et al. Patobiochemie ve schématech. Grada Publishing: Praha 2006. ISBN 80-247-1522-8.
    42. Kalousová M. Uremické toxiny - základní charakteristika. Farmakoterapie review 2014; 7: 4.
    43. Metz TO, Alderson NL, Thorpe SR et al. Pyridoxamine, an inhibitor of advanced glycation and lipoxidation reactions: a novel therapy for treatment of diabetic complications. Arch Biochem Biophys 2003; 419(1): 41-49. Go to original source... Go to PubMed...
    44. Stirban A, Negrean M, Stratmann B et al. Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes. Diabetes Care 2006; 29(9): 2064-2071. Go to original source... Go to PubMed...
    45. Vlassara H, Uribarri J, Cai W et al. Effects of sevelamer on HbA1c, inflammation, and advanced glycation end products in diabetic kidney disease. Clin J Am Soc Nephrol 2012; 7(6): 934-942. Go to original source... Go to PubMed...
    46. Ueda S, Yamagishi S, Takeuchi M et al. Oral adsorbent AST-120 decreases serum levels of AGEs in patients with chronic renal failure. Mol Med 2006; 12(7-8): 180-184. Go to original source... Go to PubMed...
    47. Coughlan MT, Forbes JM, Cooper ME. Role of the AGE crosslink breaker, alagebrium, as a renoprotective agent in diabetes. Kidney Int 2007; 72(Suppl 106): S54-S60. Go to original source... Go to PubMed...

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