9,396
Views
115
CrossRef citations to date
0
Altmetric
Research Article

Molecular strategies to prevent, inhibit, and degrade advanced glycoxidation and advanced lipoxidation end products

, , , , , , & show all
Pages 93-137 | Received 21 Feb 2013, Accepted 02 Apr 2013, Published online: 07 May 2013

References

  • Baynes JW. Role of oxidative stress in development of complication in diabetes. Diabetes 1991;40:405–412.
  • Baynes JW, Thorpe SR. Perspectives in diabetes: role of oxidative stress in diabetic complication-a new perspective on an old paradigm. Diabetes 1999;48:1–9.
  • Wohaieb SA, Godin DV. Alterations in free radical tissue-defense mechanisms in streptozotocin-induced diabetes. Diabetes 1987;36:1014–1018.
  • Lyons TJ, Silvestri G, Dunn JA, Dyer DG, Baynes JW. Role of glycation in modification of lens crystallins in diabetic andnondiabetic senile cataracts. Diabetes 1991;40: 1010–1015.
  • Brownlee M. Nonenzymatic glycosylation of macromolecules. Prospects of pharmacologic modulation. Diabetes 1992;41:57–60.
  • Monnier VM, Sell DR, Nagaraj RH, Miyata S, Grandhee S, Odetti P, Ibrahim SA. Maillard reaction-mediated molecular damage to extracellular matrix and other tissue proteins in diabetes, aging, and uremia. Diabetes 1992;41:36–41.
  • Monnier VM, Glomb M, Elgawish A, Sell DR. The mechanism of collagen cross-linking in diabetes: a puzzle nearing resolution. Diabetes 1996;45:S67–S72.
  • Monnier VM, Mustata GT, Biemel KL, Reihl O, Lederer MO, Zhenyu D, Sell DR. Cross-linking of the extracellular matrix by the maillard reaction in aging and diabetes: an update on “a puzzle nearing resolution”. Ann N Y Acad Sci 2005;1043:533–544.
  • Ghanem AA, Elewa A, Arafa LF. Pentosidine and N-carboxymethyl-lysine: biomarkers for type 2 diabetic retinopathy. Eur J Ophthalmol 2011;21:48–54.
  • Hirata K, Kubo K. Relationship between blood levels of N-carboxymethyl-lysine and pentosidine and the severity of microangiopathy in type 2 diabetes. Endocr J 2004;51: 537–544.
  • Dworacka M, Winiarska H, Szymańska M, Szczawińska K, Wierusz-Wysocka B. Serum N-epsilon-(carboxymethyl)lysine is elevated in nondiabetic coronary heart disease patients. J Basic Clin Physiol Pharmacol 2002;13:201–213.
  • Kaufmann E, Boehm BO, Süssmuth SD, Kientsch-Engel R, Sperfeld A, Ludolph AC, Tumani H. The advanced glycation end-product N epsilon-(carboxymethyl)lysine level is elevated in cerebrospinal fluid of patients with amyotrophic lateral sclerosis. Neurosci Lett 2004;371:226–229.
  • Southern L, Williams J, Esiri MM. Immunohistochemical study of N-epsilon-carboxymethyl lysine (CML) in human brain: relation to vascular dementia. BMC Neurol 2007;7:35.
  • Fukuda M, Kanou F, Shimada N, Sawabe M, Saito Y, Murayama S, et al.. Elevated levels of 4-hydroxynonenal-histidine Michael adduct in the hippocampi of patients with Alzheimer's disease. Biomed Res 2009;30:227–233.
  • Podborska M, Sevcikova A, Trna J, Dite P, Lojek A, Kubala L. Increased markers of oxidative stress in plasma of patients with chronic pancreatitis. Neuro Endocrinol Lett 2009;30:116–120.
  • Grimsrud PA, Picklo MJS, Griffin TJ, Bernlohr DA. Carbonylation of adipose proteins in obesity and insulin resistance: identification of adipocyte fatty acid-binding protein as a cellular target of 4-hydroxynonenal. Mol Cell Proteomics 2007;6:624–637.
  • Wang G, Pierangeli SS, Papalardo E, Ansari GA, Khan MF. Markers of oxidative and nitrosative stress in systemic lupus erythematosus: correlation with disease activity. Arthritis Rheum 2010;62:2064–2072.
  • Monnier VM. Intervention against the Maillard reaction in vivo. Arch Biochem Biophys 2003;419:1–15.
  • Monnier VM, Sell DR. Prevention and repair of protein d amage by the Maillard reaction in vivo. Rejuvenation Res 2006;9:264–273.
  • Ellis EM. Reactive carbonyls and oxidative stress: potential for therapeutic intervention. Pharmacol Ther 2007;115:13–24.
  • Iacobini C, Menini S, Ricci C, Scipioni A, Sansoni V, Mazzitelli G, et al.. Advanced lipoxidation end-products mediate lipid-induced glomerular injury: role of receptor-mediated mechanisms. J Pathol 2009;218:360–369.
  • Fu MX, Wells-Knecht KJ, Blackledge JA, Lyons TJ, Thorpe SR, Baynes JW. Glycation, glycosylation, and cross-linking of collagen by glucose. Kinetics, mechanims, and inhibition of the late stages of the Maillard reaction. Diabetes 1994;43:676–683.
  • Di Mario U, Pugliese G. 15th Golgi lecture: from hyperglycaemia to the dysregulation of vascular remodelling in diabetes. Diabetologia 2001;44:674–692.
  • Nishikawa T, Edelstein D, Brownlee M. The missing link: a single unifying mechanism for diabetic complications. Kidney Int 2000;58:S26–S30.
  • Augustyniak A, Bartosz G, Cipak A, Duburs G, Horáková L, Luczaj W, et al.. Natural and synthetic antioxidants: an updated overview. Free Radic Res 2010;44:1216–1262.
  • Stefek M, Drozdikova I, Vajdova K. The pyridoindole antioxidant stobadine inhibited glycation-induced absorbance and fluorescence changes in albumin. Acta Diabetol 1996; 33:35–40.
  • Stefek M, Krizanova L, Trnkova Z. Oxidative modification of serum albumin in an experimental glycation model of diabetes mellitus in vitro: Effect of the pyridoindole antioxidant stobadine. Life Sci 1999;65:1995–1997.
  • Stefek M, Sotnikova R, Okruhlicova L, Volkovova K, Kucharska J, Gajdosik A, et al.. Effect of dietary supplementation with the pyridoindole antioxidant stobadine on antioxidant state and ultrastructure of diabetic rat myocardium. Acta Diabetol 2000;37:111–117.
  • Karasu C. Glycoxidative stress and cardiovascular complications in experimentally-induced diabetes: effects of antioxidant treatment. Open Cardiovasc Med J 2010;4:240–256.
  • Stefek M, Gajdosik A, Tribulova N, Navarova J, Volkovova K, Weismann P, et al.. The pyridoindole antioxidant stobadine attenuates albuminuria, enzymuria, kidney lipid peroxidation and matrix collagen cross-linking in streptozotocin- induced diabetic rats. Meth Find Exp Clin Pharm 2002a;24: 565–571.
  • Stefek M, Tribulova N, Gajdosik A, Gajdosikova A. The pyridoindole antioxidant stobadine attenuates histochemical changes in kidney of streptozotocin-induced diabetic rats. Acta Histochem 2002b;104:413–417.
  • Cumaoglu A, Stefek M, Bauer V, Ari N, Aricioglu A, Karasu C. Glycoxidative and nitrosative stress in kidney of experimental diabetic rats: effects of the prydoindole antioxidant stobadine. Neuro Endocrinol Lett 2010;31:313–318.
  • Pekiner B, Ulusu NN, Das-Evcimen N, Sahilli M, Aktan F, Stefek M, et al.. In vivo treatment with stobadine prevents lipid peroxidation, protein glycation and calcium overload but does not ameliorate Ca2+-ATPase activity in heart and liver of streptozotocin-diabetic rats: comparison with vitamin E. Biochim Biophys Acta 2002;1588:71–78.
  • Cumaoglu A, Cevik C, Rackova L, Ari N, Karasu C. Effects of antioxidant stobadine on protein carbonylation, advanced oxidation protein products and reductive capacity of liver in streptozotocin-diabetic rats: role of oxidative/nitrosative stress. Biofactors 2007;30:171–178.
  • Demiryurek AT, Karasu C, Stefek M, Stolc S. Effect of stobadine on leukocyte free radical generation in streptozotocin-diabetic rats: comparison with vitamin E. Pharmacology 2004;70:1–4.
  • Kyselova Z, Gajdosik A, Gajdosikova A, Ulicna O, Mihalova D, Karasu C, Stefek M. Effect of the pyridoindole antioxidant stobadine on development of experimental diabetic cataract and on lens protein oxidation in rats: comparison with vitamin E and BHT. Mol Vis 2005;11:56–65.
  • Yulek F, Or M, Ozogul C, Isik AC, Ari N, Stefek M, et al.. Effects of stobadine and vitamin E in diabetes-induced retinal abnormalities: Involvement of oxidative stress. Arch Med Res 2007;38:503–511.
  • Skalska S, Kyselova Z, Gajdosikova A, Karasu C, Stefek M, Stolc S. Protective effect of stobadine on NCV in streptozotocindiabetic rats: augmentation by vitamin E. Gen Physiol Biophys 2008;27:106–114.
  • Skalska S, Kucera P, Goldenberg Z, Stefek M, Kyselova Z, Jariabka P, et al.. Neuropathy in a rat model of mild diabetes induced by multiple low doses of streptozotocin: effects of the antioxidant stobadine in comparison with a high-dose alpha-lipoic acid treatment. Gen Physiol Biophys 2010;29: 50–58.
  • Ansari NH, Bhatnagar A, Fulep E, Khanna P, Srivastava SK. Trolox protects hyperglycemia-induced cataractogenesis in cultured rat lens. Res Commun Chem Pathol Pharmacol 1994;84:93–104.
  • Srivastava SK, Ansari NH. Prevention of sugar-induced cataractogenesis in rats by butylated hydroxytoluene. Diabetes 1988;37:1505–1508.
  • Love A, Cotter MA, Cameron NE. Nerve function and regeneration in diabetic and galactosaemic rats: antioxidant and metal chelator effects. Eur J Pharmacol 1996;314:33–39.
  • Nourmohammadi I, Modarress M, Khanaki K, Shaabani M. Association of serum alpha-tocopherol, retinol and ascorbic acid with the risk of cataract development. Ann Nutr Metab 2008;52:296–298.
  • Jacques PF, Chylack LTJ, Hankinson SE, Khu PM, Rogers G, Friend J, et al.. Long-term nutrient intake and early age-related nuclear lens opacities. Arch Ophthalmol 2001; 119:1009–1019.
  • Valero MP, Fletcher AE, De Stavola BL, Vioque J, Alepuz VC. Vitamin C is associated with reduced risk of cataract in a Mediterranean population. J Nutr 2002;132: 1299–1306.
  • Cumming RG, Mitchell P, Smith W. Diet and cataract: the Blue Mountains Eye Study. Ophthalmology 2000;107: 450–456.
  • Hankinson SE, Stampfer MJ, Seddon JM, Colditz GA, Rosner B, Speizer FE, Willett WC. Nutrient intake and cataract extraction in women: a prospective study. Br Med J 1992;305:335–339.
  • Ravindran RD, Vashist P, Gupta SK, Young IS, Maraini G, Camparini M, et al.. Inverse association of vitamin C with cataract in older people in India. Ophthalmology 2011; 18:1958–1965.
  • Bors W, Michel C. Chemistry of the antioxidant. Effect of polyphenols. Ann NY Acad Sci 2002;957:57–69.
  • Amic D, Davidovic-Amic D, Beslo D, Rastija V, Lucic B, Trinajstic N. SAR and QSAR of the antioxidant activity of flavonoids. Curr Med Chem 2007;14:827–845.
  • Stefek M. Natural flavonoids as potential multifunctional agents in prevention of diabetic cataract. Interdiscip. Toxicol 2011;4:69–77.
  • Stefek M, Karasu C. Eye lens in aging and diabetes: effect of quercetin. Rejuvenation Res 2011;14:525–534.
  • Sternberg MC, Borsos AM, Roux A, Adam C, Urios P. Compared inhibition of pentosidine formation in type-I collagen incubated with glucose by catechin, myricetin, kaempferol and quercetin: role of flavonoid structure. Diabetologia 2002;45:A393–A394.
  • Odetti PR, Borgolio A, De Pascale A, Rolandi R, Adezati L. Prevention of diabetes-increased aging effect on rat collagen-linked fluorescence by aminoguanidine and rutin. Diabetes 1990;39:796–801.
  • Urios P, Kassab I, Borsos AM, Guillot R, Peyroux J, Sternberg M. Long-term treatment with a purified micronized flavonoid fraction reduces urinary albumin clearance and restores albuminemia in normotensiveand hypertensive diabetic rats. Diabetes Res Clin Pract 2000;50:S362.
  • Price DL, Rhett PM, Thorpe SR, Baynes JW. Chelating activity of advanced glycation end-product (AGE) inhibitors. J Biol Chem 2001;276:48967–48972.
  • Nagai R, Murray DB, Metz TO, Baynes JW. Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications. Diabetes 2012;61:549–559.
  • Hunt JV, Dean RT, Wolff SP. Hydroxyl radical production and autoxidative glycosylation. Glucose autoxidation as the cause of protein damage in the experimental glycation model of diabetes mellitus and ageing. Biochem J 1988; 256:205–212.
  • Hunt JV, Wolff SP. Oxidative glycation and free radical production: a causal mechanism of diabetic complications. Free Radic Res Commun 1991;1:115–123.
  • Wolff SP, Bascal ZA, Hunt JV. Autoxidative glycosylation: free radicals and glycation theory. Prog Clin Biol Res 1989;304:259–275.
  • Wolff SP, Jiang ZY, Hunt JV. Protein glycation and oxidative stress in diabetes mellitus and ageing. Free Radic Biol Med 1991;10:339–352.
  • Dunn JA, Ahmed MU, Murtiashaw MH, Richardson JM, Walla MD, Thorpe SR, Baynes JW. Reaction of ascorbate with lysine and protein under autoxidizing conditions: formation of N epsilon-(carboxymethyl)lysine by reaction between lysine and products of autoxidation of ascorbate. Biochemistry 1990;29:10964–10970.
  • Wells-Knecht MC, Thorpe SR, Baynes JW. Pathways of formation of glycoxidation products during glycation of collagen. Biochemistry 1995;34:15134–15141.
  • Smith PR, Thornalley PJ. Mechanism of the degradation of non-enzymatically glycated proteins under physiological conditions. Studies with the model fructosamine, N epsilon-(1-deoxy-D-fructos-1-yl)hippuryl-lysine. Eur J Biochem 1992;210:729–739.
  • Young IS, Tate S, Lightbody JH, McMaster D, Trimble ER. The effects of desferrioxamine and ascorbate on oxidative stress in the streptozotocin diabetic rat. Free Radic Biol Med 1995;18:833–840.
  • Schleicher ED, Wagner E, Nerlich AG. Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging. J Clin Invest 1997;99:457–468.
  • Cameron NE, Cotter MA. Rapid reversal by aminoguanidine of the neurovascular effects of diabetes in rats: modulation by nitric oxide synthase inhibition. Metabolism 1996;45: 1147–1152.
  • Zheng Y, Li XK, Wang Y, Cai L. The role of zinc, copper and iron in the pathogenesis of diabetes and diabetic complications: therapeutic effects by chelators. Hemoglobin 2008;32:135–145.
  • Urui-Adams JY, Keen CL. Copper, oxidative stress, and human health. Mol Asp Med 2005;26:268–298.
  • Lu J, Gong D, Choong SY, Xu H, Chan YK, Chen X, et al.. Copper(II)-selective chelation improves function and antioxidant defences in cardiovascular tissues of rats as a model of diabetes: comparisons between triethylenetetramine and three less copper-selective transition-metal-targeted treatments. Diabetologia 2010a;53:1217–1226.
  • Lu J. Triethylenetetramine pharmacology and its clinical applications. Mol Cancer Ther 2010b;9:2458–2467.
  • Cooper GJ. Therapeutic potential of copper chelation with triethylenetetramine in managing diabetes mellitus and Alzheimer's disease. Drugs 2011;71:1281–1320.
  • Baynes JW, Murray DB. The metal chelators, trientine and citrate, inhibit the development of cardiac pathology in the Zucker diabetic rat. Exp Diabetes Res 2009;2009:696378.
  • Gong D, Lu J, Chen X, Choong SY, Zhang S, Chan YK, et al.. Molecular changes evoked by triethylenetetramine treatment in the extracellular matrix of the heart and aorta in diabetic rats. Mol Pharmacol 2006;70:2045–2051.
  • Cooper GJ, Phillips AR, Choong SY, Leonard BL, Crossman DJ, Brunton DH, et al.. Regeneration of the heart in diabetes by selective copper chelation. Diabetes 2004; 53:2501–2508.
  • Nakamura J, Hamada Y, Chaya S, Nakashima E, Naruse K, Kato K, et al.. Transition metals and polyol pathway in the development of diabetic neuropathy in rats. Diabetes Metab Res Rev 2002;18:395–402.
  • Hamada Y, Nakashima E, Naruse K, Nakae M, Naiki M, et al.. A copper chelating agent suppresses carbonyl stress in diabetic rat lenses. J Diabetes Complications 2005;19: 328–334.
  • Nagai R, Nagai M, Shimasaki S, Baynes JW, Fujiwara Y. Citric acid inhibits development of cataracts, proteinuria and ketosis in streptozotocin (type 1) diabetic rats. Biochem Biophys Res Commun 2010;393:118–122.
  • Adrover M, Vilanova B, Frau J, Munoz F, Donoso J. The pyridoxamine action on Amadori compounds: A reexamination of its scavenging capacity and chelating effect. Bioorg Med Chem 2008;16:5557–5569.
  • Dukic-Stefanovic S, Schinzel R, Riederer P, Munch G. AGES in brain ageing: AGE-inhibitors as neuroprotective and antidementia drugs?Biogerontology 2001;2:19–34.
  • Munch G, Taneli Y, Schraven E, Schindler U, Schinzel R, Palm D, Riederer P. The cognition-enhancing drug tenilsetam is an inhibitor of protein crosslinking by advanced glycosylation. J Neural Transm Park Dis Dement Sect 1994;8:193–208.
  • Shoda H, Miyata S, Liu BF, Yamada H, Ohara T, Suzuki K, et al.. Inhibitory effects of tenilsetam on the Maillard reaction. Endocrinology 1997;138:1886–1892.
  • Hipkiss AR, Preston JE, Himsworth DT, Worthington VC, Keown M, Michaelis J, et al.. Pluripotent protective effects of carnosine, a naturally occurring dipeptide. Ann NY Acad Sci 1998;854:37–53.
  • Reddy VP, Beyaz A. Inhibitors of the Maillard reaction and AGE breakers as therapeutics for multiple diseases. Drug Discov Today 2006;11:646–654.
  • Ruggiero-Lopez D, Lecomte M, Moinet G, Patereau G, Lagarde M, Wiernsperger N. Reaction of metformin with dicarbonyl compounds. Possible implication in the inhibition of advanced glycation end produc formation. Biochem Pharmacol 1999;58:1765–1773.
  • Beisswenger P, Ruggiero-Lopez D. Metformin inhibition of glycation processes. Diabetes Metab 2003;29:6S95–103.
  • Ouslimani N, Mahrouf M, Peynet J, Bonnefont-Rousselot D, Cosson C, Legrand A, Beaudeux JL. Metformin reduces endothelial cell expression of both the receptor for advanced glycation end products and lectin-like oxidized receptor 1. Metabolism 2007;56:308–313.
  • Rahbar S, Natarajan N, Yerneni K, Scott S, Gonzales N, Nadler J. Evidence that pioglitazone, metformin and pentoxifylline are inhibitors of glycation. Clin Chim Acta 2000;301:65–77.
  • Miyata T, van Ypersele de Strihou C. Angiotensin II receptor blockers and angiotensin converting enzyme inhibitors: implication of radical scavenging and transition metal chelation in inhibition of advanced glycation endproduct formation. Arch Biochem Biophys 2003;419:50–54.
  • Figarola JL, Scott S, Loera S, Tessler C, Chu P, Weiss L, et al.. LR-90 a new advanced glycation endproduct inhibitor prevents progression of diabetic nephropathy in streptozotocin-diabetic rats. Diabetologia 2003;46:1140–1152.
  • Figarola JL, Loera S, Weng Y, Shanmugam N, Natarajan R, Rahbar S. LR-90 prevents dyslipidaemia and diabetic nephropathy in the Zucker diabetic fatty rat. Diabetologia 2008;51:882–891.
  • Bhatwadekar A, Glenn JV, Figarola JL, Scott S, Gardiner TA, Rahbar S, Stitt AW. A new advanced glycation inhibitor, LR-90, prevents experimental diabetic retinopathy in rats. Br J Ophthalmol 2008;92:545–547.
  • Figarola JL, Scott S, Loera S, Xi B, Synold T, Weiss L, Rahbar S. Prevention of early renal disease, dyslipidemia and lipid peroxidation in STZdiabetic rats by LR-9 and LR-74 novel AGE inhibitors. Diabetes Metab Res Rev 2005;21: 533–544.
  • Krautwald M, Münch G. Advanced glycation end products as biomarkers and gerontotoxins – a basis to explore methylglyoxal-lowering agents for Alzheimer's disease?Exp Gerontol 2010;45:744–751.
  • Burcham PC, Kaminskas LM, Tan D, Pyke SM. Carbonyl-scavenging drugs & protection against carbonyl stress- associated cell injury. Mini Rev Med Chem 2008;8:319–330.
  • Zhou P, Huang J, Tian F. Specific noncovalent interactions at protein-ligand interface: implications for rational drug design. Curr Med Chem 2012;19:226–238.
  • Mayr H, Bug T, Gotta MF, Hering N, Irrgang B, Janker B, et al.. Reference scales for the characterization of cationic electrophiles and neutral nucleophiles. J Am Chem.Soc 2001;123:9500–9512.
  • Cárdenas C, Rabi N, Ayers PW, Morell C, Jaramillo P, Fuentealba P. Chemical reactivity descriptors for ambiphilic reagents: dual descriptor, local hypersoftness, and electrostatic potential. J Phys Chem A 2009;113:8660–8667.
  • LoPachin RM, Gavin T, Decaprio A, Barber DS. Application of the Hard and Soft, Acids and Bases (HSAB) theory to toxicant–target interactions. Chem Res Toxicol 2012;25: 239–251.
  • Pearson RG, Songstad J. Application of the principle of hard and soft acids and bases to organic chemistry. J Am Chem Soc 1967;89:1827–1836.
  • Contreras R, Andrés J, Domingo LR, Castillo R, Pérez P. Effect of electron-withdrawing substituents on the electrophilicity of carbonyl carbons. Tetrahedron 2005;61:417–422.
  • LoPachin RM, Barber DS, Gavin T. Molecular mechanisms of the conjugated alpha,beta-unsaturated carbonyl derivatives: relevance to neurotoxicity and neurodegenerative diseases. Toxicol Sci 2008;104:235–249.
  • Halliwell B. Antioxidants in human health and disease. Annu Rev Nutr 1996;16:33–50.
  • Schafer FQ, Buettner GR. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med 2001;30: 1191–1212.
  • Blair IA. Endogenous glutathione adducts. Curr Drug Metab 2006;7:853–872.
  • Testa B, Krämer SD. The biochemistry of drug metabolism–an introduction: part 4. reactions of conjugation and their enzymes. Chem Biodivers 2008;5:2171–2336.
  • Esterbauer H, Zollner H, Scholz N. Reaction of glutathione with conjugated carbonyls. Z Naturforsch C 1975;30: 466–473.
  • Oakley A. Glutathione transferases: a structural perspective. Drug Metab Rev 2011;43:138–151.
  • Awasthi YC, Yang Y, Tiwari NK, Patrick B, Sharma A, Li J, Awasthi S. Regulation of 4-hydroxynonenal-mediated signaling by glutathione S-transferases. Free Radic Biol Med 2004;37:607–619.
  • Balogh LM, Atkins WM. Interactions of glutathione transferases with 4-hydroxynonenal. Drug Metab Rev 2011;43: 165–178.
  • Raza H. Dual localization of glutathione S-transferase in the cytosol and mitochondria: implications in oxidative stress, toxicity and disease. FEBS J 2011;278:4243–4251.
  • Balogh LM, Roberts AG, Shireman LM, Greene RJ, Atkins WM. The stereochemical course of 4-hydroxy-2-nonenal metabolism by glutathione S-transferases. J Biol Chem 2008;283:16702–16710.
  • Balogh LM, Le Trong I, Kripps KA, Shireman LM, Stenkamp RE, Zhang W, et al. Substrate specificity combined with stereopromiscuity in glutathione transferase A4-4- dependent metabolism of 4-hydroxynonenal. Biochemistry 2010;49:1541–1548.
  • Mannervik B. Molecular enzymology of the glyoxalase system. Drug Metabol Drug Interact 2008;23:13–27.
  • Thornalley PJ. Glutathione-dependent detoxification of alpha-oxoaldehydes by the glyoxalase system: involvement in disease mechanisms and antiproliferative activity of glyoxalase I inhibitors. Chem Biol Interact 1998;111–112: 137–151.
  • Wlodek L. The reaction of sulfhydryl groups with carbonyl compounds. Acta Biochim Pol 1988;35:307–317.
  • Nomi Y, Aizawa H, Kurata T, Shindo K, Nguyen CV. Glutathione reacts with glyoxal at the N-terminal. Biosci Biotechnol Biochem 2009;73:2408–2411.
  • Dodd S, Dean O, Copolov DL, Malhi GS, Berk M. N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility. Expert Opin Biol Ther 2008;8:1955–1962.
  • Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA. N-Acetylcysteine–a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol 2007;7:355–359.
  • Esterbauer H, Ertl A, Scholz N. Reaction of cysteine with alpha,beta-unsaturated aldehydes. Tetrahedron 1976;32: 285–289.
  • Wondrak GT, Cervantes-Laurean D, Roberts MJ, Qasem JG, Kim M, Jacobson EL, Jacobson MK. Identification of alpha-dicarbonyl scavengers for cellular protection against carbonyl stress. Biochem Pharmacol 2002;63:361–373.
  • Mehta R, Wong L, O’Brien PJ. Cytoprotective mechanisms of carbonyl scavenging drugs in isolated rat hepatocytes. Chem Biol Interact 2009;178:317–323.
  • Li G, Tang T, Peng M, He H, Yin D. Direct reaction of taurine with malondialdehyde: evidence for taurine as a scavenger of reactive carbonyl species. Redox Rep 2010;15: 268–274.
  • Perrett D. The metabolism and pharmacology of D-penicillamine in man. J Rheumatol Suppl 1981;7:41–50.
  • Szwergold BS. Alpha-thiolamines such as cysteine and cysteamine act as effective transglycating agents due to formation of irreversible thiazolidine derivatives. Med Hypotheses 2006;66:698–707.
  • Wondrak GT, Jacobson MK, Jacobson EL. Antimelanoma activity of apoptogenic carbonyl scavengers. J Pharmacol Exp Ther 2006;316:805–814.
  • Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta 2009;1790:1149–1160.
  • Korotchkina LG, Yang H, Tirosh O, Packer L, Patel MS. Protection by thiols of the mitochondrial complexes from 4-hydroxy-2-nonenal. Free Radic Biol Med 2001;30: 992–999.
  • Kim HY, Oi Y, Kim M, Yokozawa T. Protective effect of lipoic acid against methylglyoxal-induced oxidative stress in LLC-PK(1) cells. J Nutr Sci Vitaminol (Tokyo) 2008;54: 99–104.
  • Gorąca A, Huk-Kolega H, Piechota A, Kleniewska P, Ciejka E, Skibska B. Lipoic acid - biological activity and therapeutic potential. Pharmacol Rep 2011;63:849–858.
  • He L, Liu B, Dai Z, Zhang HF, Zhang YS, Luo XJ, et al.. Alpha lipoic acid protects heart against myocardial ischemia-reperfusion injury through a mechanism involving aldehyde dehydrogenase 2 activation. Eur J Pharmacol 2012;678: 32–38.
  • Di Simplicio P, Frosali S, Priora R, Summa D, Cherubini Di Simplicio F, Di Giuseppe D, Di Stefano A. Biochemical and biological aspects of protein thiolation in cells and plasma. Antioxid Redox Signal 2005;7:951–963.
  • Elsheikh A, Lavergne SN, Castrejon JL, Farrell J, Wang H, Sathish J, et al.. Drug antigenicity, immunogenicity, and costimulatory signaling: evidence for formation of a functional antigen through immune cell metabolism. J Immunol 2010;185:6448–6460.
  • Bolton WK, Abdel-Rahman E. Pimagedine: a novel therapy for diabetic nephropathy. Expert Opin Investig Drugs 2002;11:565–574.
  • Brownlee M, Vlassara H, Kooney A, Ulrich P, Cerami A. Aminoguanidine prevents diabetes-induced arterial wall protein crosslinking. Science 1986;232:1629–1632.
  • Vistoli G, Orioli M, Pedretti A, Regazzoni L, Canevotti R, Negrisoli G, et al.. Design, synthesis, and evaluation of carnosine derivatives as selective and efficient sequestering agents of cytotoxic reactive carbonyl species. Chem MedChem 2009;4:967–975.
  • Thornalley PJ. Use of aminoguanidine (Pimagedine) to prevent the formation of advanced glycation endproducts. Arch Biochem Biophys 2003;419:31–40.
  • Soulis-Liparota T, Cooper M, Papazoglou D, Clarke B, Jerums G. Retardation by aminoguanidine of development of albuminuria, mesangial expansion, and tissue fluorescence in streptozocin-induced diabetic rat. Diabetes 1991;40: 1328–1334.
  • Huijberts MS, Wolffenbuttel BH, Boudier HA, Crijns FR, Kruseman AC, Poitevin P, Levy BI. Aminoguanidine treatment increases elasticity and decreases fluid filtration of large arteries from diabetic rats. J Clin Invest 1993;92: 1407–1411.
  • Hammes HP, Ali SS, Uhlmann M, Weiss A, Federlin K, Geisen K, Brownlee M. Aminoguanidine does not inhibit the initial phase of experimental diabetic retinopathy in rats. Diabetologia 1995;38:269–273.
  • Hammes HP, Brownlee M, Edelstein D, Saleck M, Martin S, Federlin K. Aminoguanidine inhibits the development of accelerated diabetic retinopathy in the spontaneous hypertensive rat. Diabetologia 1994;37:32–35.
  • Swamy-Mruthinti S, Green K, Abraham EC. Inhibition of cataracts in moderately diabetic rats by aminoguanidine. Exp Eye Res 1996;62:505–512.
  • Soulis T, Cooper ME, Vranes D, Bucala R, Jerums G. Effects of aminoguanidine in preventing experimental diabetic nephropathy are related to the duration of treatment. Kidney Int 1996;50:627–634.
  • Kelly DJ, Gilbert RE, Cox AJ, Soulis T, Jerums G, Cooper ME. Aminoguanidine ameliorates overexpression of prosclerotic growth factors and collagen deposition in experimental diabetic nephropathy. J Am Soc Nephrol 2001; 12:2098–2107.
  • Thornalley PJ. Glycation in diabetic neuropathy: characteristics, consequences, causes and therapeutic options. Int. Rev. Neurobiol. 2002;50:37–57.
  • Moreau R, Nguyen BT, Doneaunu CE, Hagen TM. Reversal by aminoguanidine of the age-related increase in glycoxidation and lipoxidation in the cardiovascular system of Fischer 344 rats. Biochem Pharmacol 2005;69:29–40.
  • Chang KC, Tseng CD, Wu MS, Liang JT, Tsai MS, Cho YL, Tseng YZ. Aminoguanidine prevents arterial stiffening in a new rat model type 2 diabetes. Eur J Clin Invest 2006;36: 528–535.
  • Kern TS, Engerman RL. Pharmacological inhibition of diabetic retinopathy. Aminoguanidine and aspirin. Diabetes 2001;50:1636–1642.
  • Yagihashi S, Kamijo M, Baba M, Yagihashi N, Nagai K. Effects of aminoguanidine on functional and structural abnormalities in peripheral nerve of STZ-induced diabetic rats. Diabetes 1992;41:47–52.
  • Miyauchi Y, Shikama H, Takasu T, Okamiya H, Umeda M, Hirasaki E, et al.. Slowing of peripheral motor nerve conduction was ameliorated by aminoguanidine in streptozotocin-induced diabetic rats. Eur J Endocrinol 1996;134: 467–473.
  • Li YM, Steffes M, Donnely T, Liu C, Fuh H, Basgen J, et al.. Prevention of cardiovascular and renal pathology of aging by the advanced glycation inhibitor aminoguanidine. Proc Natl Acad Sci USA 1996;93:3902–3907.
  • Corman B, Duriez M, Poitevin P, Heudes D, Bruneval P, Tedgui A, Levy B. Aminoguanidine prevents age-related stiffening and cardiac hypertrophy. Proc Natl Acad Sci USA 1998;95:1301–1306.
  • Freedman BI, Wuerth JP, Cartwright K, Bain RP, Dippe S, Hershon K, et al.. Design and baseline characteristics for the aminoguanidine Clinical Trial in Overt Type 2 Diabetic Nephropathy (ACTIONII). Control Clin Trials 1999;20: 493–510.
  • Corbett JA, Tilton RG, Chang K, Hasan KS, Ido Y, Wang JL, et al.. Aminoguanidine, a novel inhibitor of nitric oxide formation, prevents diabetic vascular dysfunction. Diabetes 1992;41:552–556.
  • Yu PH, Zuo DM. Aminoguanidine inhibits semicarbazide-sensitive amine oxidase activity: implications for advanced glycation and diabetic complications. Diabetologia 1997; 40:1243–1250.
  • Čàsrki J, Lazarova M, Beño A. Study of β-resorcylidene aminoguanidine. I. Spectral and acid-basic properties of the onium compounds. Acta FRN Univ Comen Chimia 1978; 26:89–101.
  • Forbes JM, Soulis T, Thallas T, Panagiotopoulos S, Long DM, Vasan S, et al.. Renoprotective effects of a novel inhibitor of advanced glycation. Diabetologia 2001;44: 108–114.
  • Wilkinson-Berka JL, Kelly DJ, Koerner SM, Jaworski K, Davis B, Thallas V, Cooper ME. ALT-946 and aminoguanidine, inhibitors of advanced glycation, improve severe nephropathy in the diabetic transgenic (mREN-2)27 rat. Diabetes 2002;51:3283–3289.
  • Labieniec-Watala M, Siewiera K, Jozwiak Z. Resorcylidene aminoguanidine (RAG) improves cardiac mitochondrial bioenergetics impaired by hyperglycaemia in a model of experimental diabetes. Int J Mol Sci 2011;12:8013–8026.
  • Ruggiero-Lopez D, Lecomte M, Moinet G, Patereau G, Lagarde M, Wiernsperger N. Reaction of metformin with dicarbonyl compounds. Possible implication in the inhibition of advanced glycation end product formation. Biochem Pharmacol 1999;58:1765–1773.
  • Battah S, Ahmed N, Thornalley PJ. Kinetics and mechanism of the reaction of metformin with methylglyoxal. Int Congr Ser 2002;1245:355–356.
  • Kiho T, Kato T, Usui S, Hirano K. Effect of buformin and metformin on formation of advanced glycation end products by methylglyoxal. Clin Chim Acta 2005;358:139–145.
  • Beisswenger PJ, Howell SK, Touchette AD, Lal S, Szwergold BS. Metformin reduces systemic methylglyoxal levels in type 2 diabetes. Diabetes 1999;48:198–202.
  • Miyata T, Ueda Y, Asahi K, Izuhara Y, Inagi R, Saito A, et al.. Mechanism of the inhibitory effect of OPB-9195 [(+/2)-2-isopropylidenehydrazono-4-oxo-thiazolidin-5-yla cetanilide] on advanced glycation end product and advanced lipoxidation end product formation. J Am Soc Nephrol 2000;11:1719–1725.
  • Nakamura S, Makita Z, Ishikawa S, Yasumura K, Fujii W, Yanagisawa K, et al.. Progression of nephropathy in spontaneous diabetic rat is prevented by OPB-9195, a novel inhibitor of advanced glycation. Diabetes 1997;46:895–899.
  • Tsuchida K, Makita Z, Yamagishi S, Atsumi T, Miyoshi H, Obara S, et al.. Suppression of transforming growth factor beta and vascular endothelial growth factor in diabetic nephropathy in rats by a novel advanced glycation end product inhibitor, OPB-9195. Diabetologia 1999;42:579–588.
  • Miyata T, Ishikawa S, Asahi K, Inagi R, Suzuki D, Horie K, et al.. 2-Isopropylidenehydrazono-4-oxo-thiazolidin-5-ylacetanilide (OPB-9195) treatment inhibits the development of intimal thickening after balloon injury of rat carotid artery: Role of glycoxidation and lipoxidation reactions in vascular tissue damage. FEBS Lett 1999;445:202–206.
  • Wada R, Nishizawa Y, Yagihashi N, Takeuchi M, Ishikawa Y, Yasumura K, et al.. Effects of OPB-9195, anti-glycation agent, on experimental diabetic neuropathy. Eur J Clin Invest 2001;31:513–520.
  • Kass DA. Getting better without AGE: new insights into the diabetic heart. Circ Res 2003;92:704–706.
  • Mizutani K, Ikeda K, Tsuda K, Yamori Y. Inhibitor for advanced glycation end products formation attenuates hypertension and oxidative damage in genetic hypertensive rats. J Hypertens 2002;20:1607–1614.
  • Kochakian M, Manjula BN, Egan JJ. Chronic dosing with aminoguanidine and novel advanced glycosylation end product-formation inhibitors ameliorates cross-linking of tail tendon collagen in STZ-induced diabetic rats. Diabetes 1996;45:1694–1700.
  • O’Donnell JP. The reaction of amines with carbonyls: its significance in the nonenzymatic metabolism of xenobiotics. Drug Metab Rev 1982;13:123–159.
  • Burcham PC, Pyke SM. Hydralazine inhibits rapid acrolein-induced protein oligomerization: role of aldehyde scavenging and adduct trapping in cross-link blocking and cytoprotection. Mol Pharmacol 2006;69:1056–1065.
  • Nangaku M, Miyata T, Sada T, Mizuno M, Inagi R, Ueda Y, et al.. Anti-hypertensive agents inhibit in vivo the formation of advanced glycation end products and improve renal damage in a type 2 diabetic nephropathy rat model. J Am Soc Nephrol 2003;14:1212–1222.
  • Kandler MR, Mah GT, Tejani AM, Stabler SN, Salzwedel DM. Hydralazine for essential hypertension. Cochrane Database Syst Rev 2011;9:CD004934.
  • Bouguerne B, Belkheiri N, Bedos-Belval F, Vindis C, Uchida K, Duran H, et al.. Antiatherogenic effect of bisvanillyl-hydralazone, a new hydralazine derivative with antioxidant, carbonyl scavenger, and antiapoptotic properties. Antioxid Redox Signal 2011;14:2093–2106.
  • Galvani S, Coatrieux C, Elbaz M, Grazide MH, Thiers JC, Parini A, et al.. Carbonyl scavenger and antiatherogenic effects of hydrazine derivatives. Free Radic Biol Med 2008; 45:1457–1467.
  • Maheshwari M, Roberts JK, Desutter B, Duong KT, Tingling J, Fawver JN, et al.. Hydralazine modifies Aβ fibril formation and prevents modification by lipids in vitro. Biochemistry 2010;49:10371–11080.
  • Del Rio D, Stewart AJ, Pellegrini N. A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 2005; 15:316–328.
  • Tabrizchi R. Edaravone Mitsubishi-Tokyo. Curr Opin Investig Drugs 2000;1:347–354.
  • Pérez-González A, Galano A. On the outstanding antioxidant capacity of edaravone derivatives through single electron transfer reactions. J Phys Chem B 2012;116:1180–1188.
  • Izuhara Y, Nangaku M, Takizawa S, Takahashi S, Shao J, Oishi H, et al.. A novel class of advanced glycation inhibitors ameliorates renal and cardiovascular damage in experimental rat models. Nephrol Dial Transplant 2008; 23:497–509.
  • Lapchak PA. A critical assessment of edaravone acute ischemic stroke efficacy trials: is edaravone an effective neuroprotective therapy?Expert Opin Pharmacother 2010; 11:1753–1763.
  • Aldini G, Vistoli G, Regazzoni L, Benfatto MC, Bettinelli I, Carini M. Edaravone inhibits protein carbonylation by a direct carbonyl-scavenging mechanism: focus on reactivity, selectivity, and reaction mechanisms. Antioxid Redox Signal 2010;12:381–392.
  • Takizawa S, Izuhara Y, Kitao Y, Hori O, Ogawa S, Morita Y, et al.. A novel inhibitor of advanced glycation and endoplasmic reticulum stress reduces infarct volume in rat focal cerebral ischemia. Brain Res 2007;1183:124–137.
  • Sajithlal GB, Chithra P, Chandrakasan G. Effect of curcumin on the advanced glycation and cross-linking of collagen in diabetic rats. Biochem. Pharmacol. 1998;56:1607–1614.
  • Hu TY, Liu CL, Chyau CC, Hu ML. Trapping of methylglyoxal by curcumin in cell-free systems and in human umbilical vein endothelial cells. J Agric Food Chem 2012; 60:8190–8196.
  • LoPachin RM, Gavin T, Geohagen BC, Zhang L, Casper D, Lekhraj R, Barber DS. β-Dicarbonyl enolates: a new class of neuroprotectants. J Neurochem 2011;116:132–143.
  • Hipkiss AR. Carnosine and its possible roles in nutrition and health. Adv Food Nutr Res 2009;57:87–154.
  • Boldyrev AA. Carnosine: new concept for the function of an old molecule. Biochemistry (Mosc). 2012;77:313–326.
  • Aldini G, Carini M, Beretta G, Bradamante S, Facino RM. Carnosine is a quencher of 4-hydroxy-nonenal: through what mechanism of reaction?Biochem Biophys Res Commun 2002;298:699–706.
  • Liu Y, Xu G, Sayre LM. Carnosine inhibits (E)-4-hydroxy-2-nonenal-induced protein cross-linking: structural characterization of carnosine-HNE adducts. Chem Res Toxicol 2003;16:1589–1597.
  • Vistoli G, Carini M, Aldini G. Transforming dietary peptides in promising lead compounds: the case of bioavailable carnosine analogs. Amino Acids 2012;43:111–126.
  • Bellia F, Vecchio G, Rizzarelli E. Carnosine derivatives: new multifunctional drug-like molecules. Amino Acids 2012; 43:153–163.
  • Guiotto A, Calderan A, Ruzza P, Osler A, Rubini C, Jo DG, et al.. Synthesis and evaluation of neuroprotective alpha, beta-unsaturated aldehyde scavenger histidyl-containing analogues of carnosine. J Med Chem 2005;48:6156–6161.
  • Meredith D. The mammalian proton-coupled peptide cotransporter PepT1: sitting on the transporter-channel fence?Philos Trans R Soc Lond B Biol Sci 2009;364: 203–207.
  • Pegova A, Abe H, Boldyrev A. Hydrolysis of carnosine and related compounds by mammalian carnosinases. Comp Biochem Physiol B Biochem Mol Biol 2000;127:443–446.
  • Aldini G, Orioli M, Rossoni G, Savi F, Braidotti P, Vistoli G, et al.. The carbonyl scavenger carnosine ameliorates dyslipidaemia and renal function in Zucker obese rats. J Cell Mol Med 2011;15:1339–1354.
  • Orioli M, Vistoli G, Regazzoni L, Pedretti A, Lapolla A, Rossoni G, et al.. Design, synthesis, ADME properties, and pharmacological activities of β-alanyl-D-histidine (D-carnosine) prodrugs with improved bioavailability. ChemMedChem 2011;6:1269–1282.
  • Menini S, Iacobini C, Ricci C, Scipioni A, Blasetti Fantauzzi C, Giaccari A, et al.. D-carnosine octylester attenuates atherosclerosis and renal disease in ApoE null mice fed a Western diet through reduction of carbonyl stress and inflammation. Br J Pharmacol 2012;166:1344–1356.
  • Van Den Nest W, Domenech NA, Puche JC, Carreno Serraima C. Peptides used in the treatment and/or care of the skin, mucous membranes and/or scalp and their use in cosmetic or pharmaceutical compositions. US: Lipotec; 2011.
  • Zhao J, Zhong CJ. A review on research progress of transketolase. Neurosci Bull 2009;25:94–99.
  • Shangari N, Bruce WR, Poon R, O’Brien PJ. Toxicity of glyoxals–role of oxidative stress, metabolic detoxification and thiamine deficiency. Biochem Soc Trans 2003;31: 1390–1393.
  • Tarwadi KV, Agte VV. Effect of micronutrients on methylglyoxal-mediated in vitro glycation of albumin. Biol Trace Elem Res 2011;143:717–725.
  • Breslow R. The mechanism of thiamine action: predictions from model experiments. Ann N Y Acad Sci 1962;98: 445–452.
  • Pohl M, Sprenger GA, Müller M. A new perspective on thiamine catalysis. Curr Opin Biotechnol 2004;15: 335–342.
  • Balakumar P, Rohilla A, Krishan P, Solairaj P, Thangathirupathi A. The multifaceted therapeutic potential of benfotiamine. Pharmacol Res 2010;61:482–488.
  • Shoeb M, Ramana KV. Anti-inflammatory effects of benfotiamine are mediated through the regulation of the arachidonic acid pathway in macrophages. Free Radic Biol Med 2012;52:182–190.
  • Karachalias N, Babaei-Jadidi R, Ahmed N, Thornalley P. Accumulation of fructosyllysine and advanced glycation end products in the kidney, retina and peripheral nerve of streptozotocin-induced diabetic rats. Biochem Soc Trans 2003; 31:1423–1425.
  • Babei-Jadidi R, Karachalian N, Ahmed N, Battab S, Thornalley PJ. Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine. Diabetes 2003;52:2110–2120.
  • Stracke H, Lindemann A, Federlin K. A benfotiamine- vitamin B combination in treatment of diabetic polyneuropathy. Exp Clin Endocrinol Diabetes 1996;104:311–316.
  • Haupt E, Ledermann H, Kopcke W. Benfotiamine in the treatment of diabetic polyneuropathy-a three-week randomized, controlled pilot study (BEDIP study). Int J Clin Pharmacol Ther 2005;43:71–77.
  • Stirban A, Negrean M, Stratmann B, Gawlowski T, Horstmann T, Gotting C, 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;29:2064–2071.
  • Alkhalaf A, Klooster A, van Oeveren W, Achenbach U, Kleefstra N, Slingerland RJ, et al.. A double-blind, randomized, placebo-controlled clinical trial on benfotiamine treatment in patients with diabetic nephropathy. Diabetes Care 2010;33:1598–1601.
  • Fraser DA, Diep LM, Hovden IA, Nilsen KB, Sveen KA, Seljeflot I, Hanssen KF. The effects of long-term oral benfotiamine supplementation on peripheral nerve function and inflammatory markers in patients with type 1 diabetes: a 24-month, double-blind, randomized, placebo-controlled trial. Diabetes Care 2012;35:1095–1097.
  • Münch G, Taneli Y, Schraven E, Schindler U, Schinzel R, Palm D, Riederer P. The cognition-enhancing drug tenilsetam is an inhibitor of protein crosslinking by advanced glycosylation. J Neural Transm Park Dis Dement Sect 1994;8:193–208.
  • Webster J, Urban C, Berbaum K, Loske C, Alpar A, Gärtner U, et al.. The carbonyl scavengers aminoguanidine and tenilsetam protect against the neurotoxic effects of methylglyoxal. Neurotox Res 2005;7:95–101.
  • Jaramillo P, Perez P, Fuentealba P. Relationship between basicity and nucleophilicity. J Phys Org Chem 2007;20: 1050–1057.
  • Hall NE, Smith BJ. High-Level ab Initio molecular orbital calculations of imine formation. J Phys Chem A 1998;102:4930–4938.
  • Tahmassebi DC. Substituent effects on the stability of carbodiimides. J Chem Soc Perkin Trans 2 2001;4:613–617.
  • Shimizu M, Hachiya I, Mizota I. Conjugated imines and iminium salts as versatile acceptors of nucleophiles. Chem Comm 2009;8:874–889.
  • Voziyan PA, Hudson BG. Pyridoxamine as a multifunctional pharmaceutical: targeting pathogenic glycation and oxidative damage. Cell Mol Life Sci 2005;62:1671–1681.
  • Caldés C, Vilanova B, Adrover M, Muñoz F, Donoso J. Phenol group in pyridoxamine acts as a stabilizing element for its carbinolamines and Schiff bases. Chem Biodivers 2011;8:1318–1332.
  • Adrover M, Vilanova B, Frau J, Muñoz F, Donoso J. The pyridoxamine action on Amadori compounds: A reexamination of its scavenging capacity and chelating effect. Bioorg Med Chem 2008;16:5557–5569.
  • Nagaraj RH, Sarkar P, Mally A, Biemel KM, Lederer MO, Padayatti PS. Effect of pyridoxamine on chemical modification of proteins by carbonyls in diabetic rats: characterization of a major product from the reaction of pyridoxamine and methylglyoxal. Arch Biochem Biophys 2002;402:110–119.
  • Kang Z, Li H, Li G, Yin D. Reaction of pyridoxamine with malondialdehyde: mechanism of inhibition of formation of advanced lipoxidation end-products. Amino Acids 2006; 30:55–61.
  • Amarnath V, Amarnath K, Amarnath K, Davies S, Roberts LJ II. Pyridoxamine: an extremely potent scavenger of 1,4-dicarbonyls. Chem Res Toxicol 2004;17:410–415.
  • Adrover M, Vilanova B, Muñoz F, Donoso J. Unexpected isomeric equilibrium in pyridoxamine Schiff bases. Bioorg Chem 2009;37:26–32.
  • Adrover M, Vilanova B, Frau J, Muñoz F, Donoso J. A comparative study of the chemical reactivity of pyridoxamine, Ac-Phe-Lys and Ac-Cys with various glycating carbonyl compounds. Amino Acids 2009;36:437–448.
  • Mehansho H, Buss DD, Hamm MW, Henderson LM. Transport and metabolism of pyridoxine in rat liver. Biochim Biophys Acta 1980;631:112–123.
  • Stitt A, Gardiner TA, Alderson NL, Canning P, Frizzell N, Duffy N, et al.. The AGE inhibitor pyridoxamine inhibits development of retinopathy in experimental diabetes. Diabetes 2002;51:2826–2832.
  • Degenhardt TP, Alderson NL, Arrington DD, Beattie RJ, Basgen JM, Steffes MW, et al.. Pyridoxamine inhibits early renal disease and dyslipidemia in the streptozotocin-diabetic rat. Kidney Int 2002;61:939–950.
  • Nakamura S, Li H, Adijiang A, Pischetsrieder M, Niwa T. Pyridoxal phosphate prevents progression of diabetic nephropathy. Nephrol Dial Transplant 2007;22: 2165–2174.
  • Forbes JM, Thallas-Bonke V, Cooper ME, Merlin TC. Advanced glycation: how are we progressing to combat this web of sugar anomalies in diabetic nephropathy. Curr Pharm Des 2004;10:3361–3372.
  • Williams ME, Bolton WK, Khalifah RG, Degenhardt TP, Schotzinger RJ, McGill JB. Effects of pyridoxamine in combined phase 2 studies of patients with type 1 and type 2 diabetes and overt nephropathy. Am J Nephrol 2007;27: 605–614.
  • Sasaki NA, Garcia-Alvarez MC, Wang Q, Ermolenko L, Franck G, Nhiri N, et al.. N-Terminal 2,3-diaminopropionic acid (Dap) peptides as efficient methylglyoxal scavengers to inhibit advanced glycation endproduct (AGE) formation. Bioorg Med Chem 2009;17:2310–2320.
  • Audic N, Potier G, Sasaki NA. New 2,3-diaminopropionic acid inhibitors of AGE and ALE formation. Org Biomol Chem 2012; Dec 17 [Epub ahead of print].
  • Soulis T, Sastra S, Thallas V, Mortensen SB, Wilken M, Clausen JT, et al.. A novel inhibitor of advanced glycation end-product formation inhibits mesenteric vascular hypertrophy in experimental diabetes. Diabetologia 1999;42:472–479.
  • Oturai PS, Christensen M, Rolin B, Pedersen KE, Mortensen SB, Boel E. Effects of advanced glycation end-product inhibition and cross-link breakage in diabetic rats. Metabolism 2000;49:996–1000.
  • Silva PJ. Inductive and resonance effects on the acidities of phenol, enols, and carbonyl alpha-hydrogens. J Org Chem 2009;74:914–916.
  • Lo CY, Hsiao WT, Chen XY. Efficiency of trapping methylglyoxal by phenols and phenolic acids. J Food Sci 2011; 76:H90–H96.
  • Wang Y, Ho CT. Flavour chemistry of methylglyoxal and glyoxal. Chem Soc Rev 2012;41:4140–4149.
  • Wu CH, Yen GC. Inhibitory effect of naturally occurring flavonoids on the formation of advanced glycation endproducts. J Agric Food Chem 2005;53:3167–3173.
  • Lo CY, Li S, Tan D, Pan MH, Sang S, Ho CT. Trapping reactions of reactive carbonyl species with tea polyphenols in simulated physiological conditions. Mol Nutr Food Res 2006;50:1118–1128.
  • Sang S, Shao X, Bai N, Lo CY, Yang CS, Ho CT. Tea polyphenol (-)-epigallocatechin-3-gallate: a new trapping agent of reactive dicarbonyl species. Chem Res Toxicol 2007;20:1862–1870.
  • Lv L, Shao X, Chen H, Ho CT, Sang S. Genistein inhibits advanced glycation end product formation by trapping methylglyoxal. Chem Res Toxicol 2011;24:579–586.
  • Shao X, Bai N, He K, Ho CT, Yang CS, Sang S. Apple polyphenols, phloretin and phloridzin: new trapping agents of reactive dicarbonyl species. Chem Res Toxicol 2008; 21:2042–2050.
  • Matsuda H, Wang T, Managi H, Yoshikawa M. Structural requirements of fl avonoids for inhibition of protein glycation and radical scavenging activities. Bioorg Med Chem 2003; 11:5317–5323.
  • Beretta G, Furlanetto S, Regazzoni L, Zarrella M, Facino RM. Quenching of alpha,beta-unsaturated aldehydes by green tea polyphenols: HPLC-ESI-MS/MS studies. J Pharm Biomed Anal 2008;48:606–611.
  • Lv L, Shao X, Wang L, Huang D, Ho CT, Sang S. Stilbene glucoside from Polygonum multiflorum Thunb.: a novel natural inhibitor of advanced glycation end product formation by trapping of methylglyoxal. J Agric Food Chem 2010;58:2239–2245.
  • Nakajima Y, Inokuchi Y, Shimazawa M, Otsubo K, Ishibashi T, Hara H. Astaxanthin, a dietary carotenoid, protects retinal cells against oxidative stress in-vitro and in mice in-vivo. J Pharm Pharmacol 2008;60:1365–1374.
  • Peng X, Ma J, Chao J, Sun Z, Chang RC, Tse I, et al.. Beneficial effects of cinnamon proanthocyanidins on the formation of specific advanced glycation endproducts and methylglyoxal-induced impairment on glucose consumption. J Agric Food Chem 2010;58:6692–6696.
  • Fodor G, Arnold R, Mohacsi T, Karle I, Flippen-Anderson J. A new role for l-ascorbic acid: Michael donor to alpha, beta-unsaturated carbonyl compounds. Tetrahedron 1983;39: 2137–2145.
  • Miranda CL, Reed RL, Kuiper HC, Alber S, Stevens JF. Ascorbic acid promotes detoxification and elimination of 4-hydroxy-2(E)-nonenal in human monocytic THP-1 cells. Chem Res Toxicol 2009;22:863–874.
  • Kesinger NG, Langsdorf BL, Yokochi AF, Miranda CL, Stevens JF. Formation of a vitamin C conjugate of acrolein and its paraoxonase-mediated conversion into 5,6,7,8- tetrahydroxy-4-oxooctanal. Chem Res Toxicol 2010;23: 836–844.
  • Huby R, Harding JJ. Non-enzymic glycosylation (glycation) of lens proteins and protection by aspirin and reduced glutathione. Exp Eye Res 1988;47:53–59.
  • Swamy MS, Abraham EC. Inhibition of lens crystallin glycation and high molecular weight aggregate formation by aspirin in vitro and in vivo. Invest. Ophthalmol Visual Sci 1989;30:1120–1126.
  • Ajiboye R, Harding JJ. The non-enzymic glycosylation of bovine lens proteins by glucosamine and its inhibition by aspirin, ibuprofen and glutathione. Exp Eye Res 1989;49: 31–41.
  • Crompton M, Rixon KC, Harding JJ. Aspirin prevents carbamylation of soluble lens proteins and prevents cyanate-induced phase separation opacities in vitro: a possible mechanism by which aspirin could prevent cataract. Exp Eye Res 1985;40:297–311.
  • Rao GN, Lardis MP, Cotlier E. Acetylation of lens crystallins: a possible mechanism by which aspirin could prevent cataract formation. Biochem Biophys Res Commun 1985;128:1125–1132.
  • Rao GN, Cotlier E. Aspirin prevents the nonenzymic glycosylation and carbamylation of the human eye lens crystallins in vitro. Biochem Biophys Res Commun 1988;151:991–996.
  • Blakytny R, Harding JJ. Prevention of cataract in diabetic rats by aspirin, paracetamol (acetaminophen) and ibuprofen. Exp Eye Res 1992;54:509–518.
  • Zhao W, Devamanoharan PS, Varma SD. Fructose induced deactivation of glucose-6-phosphate dehydrogenase activity and its prevention by pyruvate: implications in cataract prevention. Free Radic Res Commun 1998;29:315–320.
  • Zhao W, Devamanoharan PS, Varma SD. Fructose-mediated damage to lens α-crystallin: prevention by pyruvate. Biochim Biophys Acta 2000a;1500:161–168.
  • Devamanoharan PS, Ali AH, Varma SD. Non-enzymatic glycation of lens proteins and haemoglobin-inhibition by pyruvate: an in-vivo study. Diabetes Obes Metab 1999;1: 159–164.
  • Hegde KR, Varma SD. Prevention of cataract by pyruvate in experimentally diabetic mice. Mol Cell Biochem 2005;269:115–120.
  • Yabe-Nishimura C. Aldose reductase in glucose toxicity: a potential target for the prevention of diabetic complications. Pharmacol Rev 1998;50:21–33.
  • Tsukushi S, Katsuzaki T, Aoyama I, Takayama F, Miyazaki T, Shimokata K, Niwa T. Increased erythrocyte 3-DG and AGEs in diabetic hemodialysis patients: role of the polyol pathway. Kidney Int 1999;55:1970–1976.
  • Hamada Y, Nakamura J, Naruse K, Komori T, Kato K, Kasuya Y, et al.. Epalrestat, an aldose reductase ihibitor, reduces the levels of Nepsilon-(carboxymethyl)lysine protein adducts and their precursors in erythrocytes from diabetic patients. Diabetes Care 2000;23:1539–1544.
  • Nakamura N, Yamazaki K, Satoh A, Urakaze M, Kobayashi M, Yamabe H, et al.. Effects of eparlestat on plasma levels of advanced glycation end products in patients with type 2 diabetes. In Vivo 2003;17:177–180.
  • Kawai T, Takei I, Tokui M, Funae O, Miyamoto K, Tabata M, et al.. Effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy in patients with type 2 diabetes, in relation to suppression of N(epsilon)-carboxymethyl lysine. J Diabetes Complications 2010;24: 424–432.
  • Hallam KM, Li Q, Ananthakrishnan R, Kalea A, Zou YS, Vedantham S, et al.. Aldose reductase and AGE-RAGE pathways: central roles in the pathogenesis of vascular dysfunction in aging rats. Aging Cell 2010;9:776–784.
  • Delpierre G, Rider MH, Collard F, Stroobant V, Vanstapel F, Santos H, Van Schaftingen E. Identification, cloning, and heterologous expression of a mammalian fructosamine-3-kinase. Diabetes 2000;49:1627–1634.
  • Szwergold BS, Howell S, Beisswenger PJ. Human fructosamine-3-kinase. Purification, sequencing, substrate specificity, and evidence of activity in vivo. Diabetes 2001;50: 2139–2147.
  • Delpierre G, Collard F, Fortpied J, Van Schaftingen E. Fructosamine 3-kinase is involved in an intracellular deglycation pathway in human erythrocytes. Biochem J 2002;365:801–808.
  • Delpierre G, Van Schaftingen E. Fructosamine 3-kinase, an enzyme involved in protein deglycation. Biochem Soc Trans 2003;31:1354–1357.
  • Delpierre G, Vertommen D, Communi D, Rider MH, Van Schaftingen E. Identification of fructosamine redues deglycated by fructosamine-3-kinase in human hemoglobin. J Biol Chem 2004;279:27613–27620.
  • Veiga-da-Cunha M, Jacquemin P, Delpierre G, Godfraind C, Theate I, Vertommen D, et al.. Increased protein glycation in fructosamine 3-kinase-deficient mice. Biochem J 2006;399:257–264.
  • Pascal SMA, Veiga-da-Cunha M, Gilon P, Van Schaftingen E, Jonas JC. Effects of fructosamine-3-kinase deficiency on function and survival of mouse pancreatic islets after prolonged culture in high glucose or robose concentrations. Am J Physiol Endocrinol Metab 2010;298:E586–E596.
  • Van Schaftingen E, Collard F, Wiame E, Veiga-da-Cunha M. Enzymatic repair of Amadori products. Amino Acids 2012; 42:1143–1150.
  • Delplanque J, Delpierre G, Opperdoes FR, Van Schaftingen E. Tissue distribution and evolution of fructosamine 3-kinase and fructosamine 3-kinase-related protein. J Biol Chem 2004;279:46606–46613.
  • Van Schaftingen E, Delpierre G, Collard F, Fortpied J, Gemayel R, Wiame E, Veiga-da-Cunha M. Fructosamine 3-kinase and other enzymes involved in protein deglycation. Adv Enzyme Regul 2007;47:261–269.
  • Deppe VM, Bongaerts J, O’Connell T, Maurer KH, Meinhardt F. Enzymatic deglycation of Amadori products in bacteria: mechanisms, occurrence and physiological functions. Appl Microbiol Biotechnol 2011;90:399–406.
  • Thornalley PJ. Dicarbonyl intermediates in the Maillard reaction. Ann NY Acad Sci 2005;1043:111–117.
  • Thornalley PJ. Protein and nucleotide damage by glyoxal and methylglyoxal in physiological systems – role in ageing and disease. Drug Metabol Drug Interact 2008;23:125–150.
  • Hydman D, Bauman DR, Heredia VV, Penning TV. The aldo-keto reductase superfamily homepage. Chem Biol Interact 2003;143–144:621–631.
  • Petrash JM. All in the family:aldose reductase and closely related aldo-keto reductases. Cell Mol Life Sci 2004;61: 737–749.
  • Ansari NH, Bhatnagar A., Liu SQ, Srivastava SK. Purification and characterization of aldose reductase and aldehyde reductase from human kidney. Biochem Int 1991; 25:755–765.
  • Das B, Srivastava SK. Purification and properties of aldose reductase and aldehyde reductase II from human erythrocyte. Arch Biochem Biophys 1985;238:670–679.
  • Morjana NA, Flynn TG. Aldose reductase from human psoas muscle. Purification, substrate specificity, immunological characterization, and effect of drugs and inhibitors. J Biol Chem 1989;264:2906–2911.
  • Srivastava SK, Ansari NH, Hair GA, Das B. Aldose and aldehyde reductases in human tissues. Biochim Biophys Acta 1984;800:220–227.
  • van der Jagt DL, Hunsaker LA, Robinson B, Stangebye LA, Deck LM. Aldehyde and aldose reductases from human placenta. Heterogenous expression of multiple enzyme forms. J Biol Chem 1990;265:10912–10918.
  • van der Jagt DL, Robinson B, Taylor KK, Hunsaker LA. Aldose reductase from human skeletal and heart muscle. Interconvertible forms related by thiol-disulfide exchange. J Biol Chem 1990;265:20982–20987.
  • Wermuth B, Burgisser H, Bohren K, von Wartburg JP. Purification and characterization of humain brain aldose reductase. Eur J Biochem 1982;127:279–284.
  • Kumar PA, Reddy GB. Focus on molecules: aldose reductase. Exp Eye Res 2007;85:739–740.
  • Borhani DW, Harter TM, Petrash JM. The crystal structure of the aldose reductase NADPH binary complex. J Biol Chem 1992;267:24841–24847.
  • Wilson DK, Bohren KM, Gabbay KH, Quiocho FA. An unlikely sugar substrate site in the 1.65 A structure of the human aldose reductase holoenzyme implicated in diabetic complications. Science 1992;257:81–84.
  • Srivastava S, Watowich SJ, Petrash JM, Srivastava SK, Bhatnagar A. Structural and kinetic determinants of aldehyde reduction by aldose reductase. Biochemistry 1999;38: 42–54.
  • Shen YI, Zhong L, Johnson S, Cao D. Human aldo-keto reductases 1B1 and 1B10; a comparative study of their enzyme activity toward electrophilic carbonyl compounds. Chem Biol Interact 2011;191:192–198.
  • Vander Jagt DL, Robinson B, Taylor KK, Hunsaker LA. Reduction of trioses by NADPH-dependent aldo-keto reductases. Aldose reductase, methylglyoxal and diabetic complications. J Biol Chem 1992;267:4364–4369.
  • Vander Jagt DL, Hassebrook RK, Hunsaker LA, Brown WM, Royer R. Metabolism of the 2-oxoaldehyde methylglyoxal by aldose reductase and by glyoxalase-I: roles for glutathione in both enzymes and implications for diabetic complications. Chem Biol Interact 2001;130–132:549–562.
  • Yabe-Nishimura C, Nishinaka T, Iwata K, Seo HG. Up-regulation of aldose reductase by the substrate, methylglyoxal. Chem Biol Interact 2003;143–144:317–323.
  • Baba SP, Barski OA, Ahmed Y, O’Toole TE, Conklin DJ, Bhatnagar A, Srivastava S. Reductive metabolism of AGE precursors: a metabolic route for preventing AGE accumulation in cardiovascular tissue. Diabetes 2009;58:2486–2497.
  • Baba SP, Hellmann J, Srivastava S, Bhatnagar A. Aldose reductase (AKR1B3) regulates the accumulation of advanced glycosylation end products (AGEs) and the expression of AGE receptor (RAGE). Chem Biol Interact 2011;191: 357–363.
  • Sakiyama H, Takahashi M, Yamamoto T, Teshima T, Lee SH, Miyamoto Y, et al.. The internalization and metabolism of 3-deoxyglucosone in human umbilical vein endothelial cells. J Biochem 2006;139:245–253.
  • Thornalley PJ. Glyoxalase I – structure, function and a critical role in the enzymatic defence against glycation. Biochem Soc Trans 2003;31:1343–1348.
  • Grillo MA, Colombatto S. Advanced glycation end-products (AGEs): involment in aging and in neurodegenerative diseases. Amino Acids 2008;35:29–36.
  • Xue M, Rabbani N, Thornalley PJ. Glyoxalase in ageing. Semin Cell Dev Biol 2011;22:293–301.
  • Marasinghe GPK, Sander IM, Bennett B, Periyannan G, Yang KW, Makaroff CA, Crowder MW. Structural studies on a mitochondrial glyoxalase II. J Biol Chem 2005;280: 40668–40675.
  • Shinohara M, Thornalley PJ, Giardino I, Beisswenger P, Thorpe SR, Onorato J, Brownlee M. Overexpression of glyoxalase-I in bovine endothelial cell inhibits intracellular advanced glycation endproduct formation and prevents hyperglycemia-induced increases in macromolecular endocytosis. J Clin Invest 1998;101:1142–1147.
  • Brouwers O, Niessen PM, Ferreira I, Miyata T, Scheffer PG, Teerlink T, et al.. Overexpression of glyoxalase-I reduces hyperglycemia-induced levels of advanced glycation end products and oxidative stress in diabetic rats. J Biol Chem 2011;286:1374–1380.
  • Miller AG, Smith DG, Bhat M, Nagaraj RH. Glyoxalase I is critical for human retinal capillary pericyte survival under hyperglycemic conditions. J Biol Chem 2006;281: 11864–11887.
  • Kumagai T, Nangaku M, Kojima I, Nagai R, Ingelfinger JR, Miyata T, et al.. Glyoxalase I overexpression ameliorates renal ischemia-reperfusion injury in rats. Am J Physiol Renal Physiol 2009;296:F912–F921.
  • Inagi R, Kumagai T, Nangaku M. The role of glyoxalase system in renal hypoxia. Adv Exp Med Biol 2010;662: 49–55.
  • Mailankot M, Padmanabha S, Pasupuleti N, Major D, Howell S, Nagaraj RH. Glyoxalase I activity and immunoreactivity in the aging human lens. Biogerontology 2009;10:711–720.
  • Piec I, Listrat A, Alliot J, Chambon C, Taylor RG, Bechet D. Differential proteome analysis of aging in rat skeletal muscle. FASEB J 2005;19:1143–1145.
  • Kuhla B, Boeck K, Luth HJ, Schmidt A, Weigle B, Schmitz M, et al.. Age-dependent changes of glyoxalase I expression in human brain. Neurobiol Aging 2006;27: 815–822.
  • Kuhla B, Luth HJ, Haferburg D, Boeck K, Arendt T, Munch G. Methylglyoxal, glyoxal and their detoxification in Alzheimer's disease. Ann NY Acad Sci 2005;1043:211–216.
  • Kuhla B, Boeck K, Schmidt A, Ogunlade V, Arendt T, Munch G, Luth HJ. Age-and stage-dependent glyoxalase I expression and its activity in normal and Alzheimer's disease. Neurobiol Aging 2007;28:29–41.
  • Rabbani N, Thornalley PJ. Glycation research in amino acids: a place to call home. Amino Acids 2012;42:1087–1096.
  • Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: a review. Diabetologia 2001;44:129–146.
  • Goldberg T, Cai W, Peppa M, Dardaine V, Baliga BS, Uribarri J, Vlassara H. Advanced glycoxidation end products in commonly consumed foods. J Am Diet Assoc 2004;104: 1287–1291.
  • Foerster A, Henle T. Glycation in food and metabolic transit of dietary AGEs (advanced glycation end-products): studies on the urinary excretion of pyrraline. Biochem Soc Trans 2003;31:1383–1385.
  • Ravikumar B, Sarkar S, Davies JE, Futter M, Garcia- Arencibia M, Green-Thompson ZW, et al.. Regulation of mammalian autophagy in physiology and pathophysiology. Physiol Rev 2010;90:1383–1435.
  • Grimm S, Höhn A, Grune T. Oxidative protein damage and the proteasome. Amino Acids 2012a;42:23–38.
  • Jung T, Höhn A, Catalgol B, Grune T. Age-related differences in oxidative protein damage in young and senescent fibroblasts. Arch Biochem Biophys 2009;483:127135.
  • Castro JP, Ott C, Jung T, Grune T, Almeida H. Carbonylation of the cytoskeletal protein actin leads to aggregate formation. Free Radic Biol Med 2012;53:916–925.
  • Kueper T, Grune T, Prahl S, Lenz H, Welge V, Biernoth T, et al.. Vimentin is a specific target in skin glycation. J Biol Chem 2007;282:23427–23436.
  • Dunlop RA, Brunk UT, Rodgers KJ. Oxidized proteins: mechanisms of removal and consequences of accumulation. IUBMB Life 2009;61:522–527.
  • Rajawat YS, Hilioti Z, Bossis I. Aging: central role for autophagy and the lysosomal degradative system. Ageing Res Rev 2009;8:199–213.
  • De Duve C, Wattiaux R. Functions of lysosomes. Annu Rev Physiol 1966;28:435–492.
  • Luzio JP, Pryor PR, Bright NA. Lysosomes: fusion and function. Nat Rev Mol Cell Biol 2007;8:622–632.
  • Mellman I, Fuchs R, Helenius AW. Acidification of the endocytic and exocytic pathways. Annu Rev Biochem 1986; 55:663–700.
  • Horiuchi S, Sakamoto Y, Sakai M. Scavenger receptors for oxidized and glycated proteins. Amino Acids 2003;25: 283–292.
  • Bierhaus A, Humpert PM, Morcos M, Wendt T, Chavakis T, Arnold B, et al.. Understanding RAGE, the receptor for advanced glycation end products. J Mol Med 2005;83: 876–886.
  • Ramasamy R, Yan SF, Schmidt AM. Arguing for the motion: yes, RAGE is a receptor for advanced glycation endproducts. Mol. Nutr. Food Res. 2007;51:1111–1115.
  • Ohgami N, Nagai R, Ikemoto M, Arai H, Kuniyasu A, Horiuchi S, Nakayama H. Cd36, a member of the class b scavenger receptor family, as a receptor for advanced glycation end products. J Biol Chem 2001;276:3195–3202.
  • Vlassara H, Li YM, Imani F, Wojciechowicz D, Yang Z, Liu FT, Cerami A. Identification of galectin-3 as a high- affinity binding protein for advanced glycation end products (AGE): a new member of the AGE-receptor complex. Mol Med 1995;1:634–646.
  • Stolzing A, Grune T. Neuronal apoptotic bodies: phagocytosis and degradation by primary microglial cells. FASEB J 2004;18:743–745.
  • Araki N, Higashi T, Mori T, Shibayama R, Kawabe Y, Kodama T, et al.. Macrophage scavenger receptor mediates the endocytic uptake and degradation of advanced glycation end products of the Maillard reaction. Eur J Biochem 1995;230:408–415.
  • Grimm S, Ott C, Hörlacher M, Weber D, Höhn A, Grune T. Advanced glycation end products-induced formation of immunoproteasomes: involvement of the receptor for AGEs and Jak2/STAT1. Biochem J 2012b;448:127–139.
  • Miyata S, Liu BF, Shoda H, Ohara T, Yamada H, Suzuki K, Kasuga M. Accumulation of pyrraline-modified albumin in phagocytes due to reduced degradation by lysosomal enzymes. J Biol Chem 1997;272:4037–4042.
  • Saito A, Nagai R, Tanuma A, Hama H, Cho K, Takeda T, et al.. Role of megalin in endocytosis of advanced glycation end products: implications for a novel protein binding to both megalin and advanced glycation end products. J Am Soc Nephrol 2003;14:1123–1131.
  • Stolzing A, Widmer R, Jung T, Voss P, Grune T. Degradation of glycated bovine serum albumin in microglial cells. Free Radic Biol Med 2006;40:1017–1027.
  • Grimm S, Ernst L, Grötzinger N, Höhn A, Breusing N, Reinheckel T, Grune T. Cathepsin D is one of the major enzymes involved in intracellular degradation of AGE- modified proteins. Free Radic Res 2010;44:1013–1026.
  • Grimm S, Horlacher M, Catalgol B, Hoehn A, Reinheckel T, Grune T. Cathepsins D and L reduce the toxicity of advanced glycation end products. Free Radic Biol Med 2012c;52: 1011–1023.
  • Grune T, Jung T, Merker K, Davies KJ. Decreased proteolysis caused by protein aggregates, inclusion bodies, plaques, lipofuscin, ceroid, and ‘aggresomes’ during oxidative stress, aging, and disease. Int J Biochem Cell Biol 2004;36: 2519–2530.
  • Grune T, Merker K, Sandig G, Davies KJ. Selective dregradation of oxidatively modified protein substrates by the proteasome. Biochem Biophys Res Commun 2003;305: 709–718.
  • Kopito RR. Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol 2000;10:524–530.
  • Liscic RM, Grinberg LT, Zidar J, Gitcho MA, Cairns NJ. ALS and FTLD: two faces of TDP-43 proteinopathy. Eur J Neurol 2008;15:772–780.
  • Bennett EJ, Shaler TA, Woodman B, Ryu KY, Zaitseva TS, Becker CH, et al.. Global changes to the ubiquitin system in Huntington's disease. Nature 2007;448:704–708.
  • Tan JM, Wong ES, Kirkpatrick DS, Pletnikova O, Ko HS, Tay SP, et al.. Lysine 63-linked ubiquitination promotes the formation and autophagic clearance of protein inclusions associated with neurodegenerative diseases. Hum Mol Genet 2008;17:431–439.
  • Yamamoto A, Simonsen A. The elimination of accumulated and aggregated proteins: a role for aggrephagy in neurodegeneration. Neurobiol Dis 2011;43:17–28.
  • Chondrogianni N, Gonos ES. Proteasome function determines cellular homeostasis and the rate of aging. Adv Exp Med Biol 2010;694:38–46.
  • Chondrogianni N, Gonos ES. Structure and function of the ubiquitin-proteasome system: modulation of components. Prog Mol Biol Transl Sci 2012;109:41–74.
  • Goldberg AL. Functions of the proteasome: from protein degradation and immune surveillance to cancer therapy. Biochem Soc Trans 2007;35:12–17.
  • Sijts EJ, Kloetzel PM. The role of the proteasome in the generation of MHC class I ligands and immune responses. Cell Mol Life Sci 2011;68:1491–1502.
  • Angeles A, Fung G, Luo H. Immune and non-immune functions of the immunoproteasome. Front Biosci 2012;17: 1904–1916.
  • Pickering AM, Koop AL, Teoh CY, Ermak G, Grune T, Davies KJ. The immunoproteasome, the 20S proteasome and the PA28αβ proteasome regulator are oxidative-stress-adaptive proteolytic complexes. Biochem J 2010;432:585–594.
  • Seifert U, Bialy LP, Ebstein F, Bech-Otschir D, Voigt A, Schröter F, et al.. Immunoproteasomes preserve protein homeostasis upon interferon-induced oxidative stress. Cell 2010;142:613–624.
  • Ciechanover A. Intracellular protein degradation: from a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting. Cell Death Differ 2005;12:1178–1190.
  • Bulteau AL, Verbeke P, Petropoulos I, Chaffotte AF, Friguet B. Proteasome inhibition in glyoxal-treated fibroblasts and resistance of glycated glucose-6-phosphate dehydrogenase to 20 S proteasome degradation in vitro. J Biol Chem 2001;276:45662–45668.
  • Cervantes-Laurean D, Roberts MJ, Jacobson EL, Jacobson MK. Nuclear proteasome activation and degradation of carboxymethylated histones in human keratinocytes following glyoxal treatment. Free Radic Biol Med 2005; 38:786–795.
  • Uchiki T, Weikel KA, Jiao W, Shang F, Caceres A, Pawlak D, et al.. Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in nondiabetics). Aging Cell 2012; 11:1–13.
  • Moheimani F, Morgan PE, van Reyk DM, Davies MJ. Deleterious effects of reactive aldehydes and glycated proteins on macrophage proteasomal function: possible links between diabetes and atherosclerosis. Biochim Biophys Acta 2010;1802:561–571.
  • Chondrogianni N, Gonos ES. Proteasome activation as a novel antiaging strategy. IUBMB Life 2008;60:651–655.
  • Chondrogianni N, Petropoulos I, Grimm S, Georgila K, Catalgol B, Friguet B, et al.. Protein damage, repair and proteolysis. Mol Aspects Med 2012;in press.
  • Gaczynska M, Rock KL, Spies T, Goldberg AL. Peptidase activities of proteasomes are differentially regulated by the major histocompatibility complex-encoded genes for LMP2 and LMP7. Proc Natl Acad Sci USA 1994;91:9213–9217.
  • Gaczynska M, Goldberg AL, Tanaka K, Hendil KB, Rock KL. Proteasome subunits X and Y alter peptidase activities in opposite ways to the interferon-gamma-induced subunits LMP2 and LMP7. J Biol Chem 1996;271: 17275–17280.
  • Chondrogianni N, Tzavelas C, Pemberton AJ, Nezis IP, Rivett AJ, Gonos ES. Overexpression of proteasome beta5 assembled subunit increases the amount of proteasome and confers ameliorated response to oxidative stress and higher survival rates. J Biol Chem 2005;280:11840–11850.
  • Liu Y, Liu X, Zhang T, Luna C, Liton PB, Gonzalez P. Cytoprotective effects of proteasome beta5 subunit overexpression in lens epithelial cells. Mol Vis 2007;13:31–38.
  • Kwak MK, Cho JM, Huang B, Shin S, Kensler TW. Role of increased expression of the proteasome in the protective effects of sulforaphane against hydrogen peroxide-mediated cytotoxicity in murine neuroblastoma cells. Free Radic Biol Med 2007;43:809–817.
  • Hwang JS, Chang I, Kim S. Age-associated decrease in proteasome content and activities in human dermal fibroblasts: restoration of normal level of proteasome subunits reduces aging markers in fibroblasts from elderly persons. J Gerontol A Biol Sci Med Sci 2007;62:490–499.
  • Chondrogianni N, Gonos ES. Overexpression of hUMP1/POMP proteasome accessory protein enhances proteasome-mediated antioxidant defence. Exp Gerontol 2007;42: 899–903.
  • Chen Q, Thorpe J, Dohmen JR, Li F, Keller JN. Ump1 extends yeast lifespan and enhances viability during oxidative stress: central role for the proteasome?Free Radic Biol Med 2006;40:120–126.
  • Hirano Y, Kaneko T, Okamoto K, Bai M, Yashiroda H, Furuyama K, et al.. Dissecting beta-ring assembly pathway of the mammalian 20S proteasome. EMBO J 2008;27: 2204–2213.
  • Rosenzweig R, Glickman MH. Forging a proteasome alpha-ring with dedicated proteasome chaperones. Nat Struct Mol Biol 2008;15:218–220.
  • Mannhaupt G, Schnall R, Karpov V, Vetter I, Feldmann HW. Rpn4p acts as a transcription factor by binding to PACE, a nonamer box found upstream of 26S proteasomal and other genes in yeast. FEBS Lett 1999;450:27–34.
  • Ju D, Wang L, Mao X, Xie Y. Homeostatic regulation of the proteasome via an Rpn4-dependent feedback circuit. Biochem Biophys Res Commun 2004;321:51–57.
  • Hahn JS, Neef DW, Thiele DJ. A stress regulatory network for co-ordinated activation of proteasome expression mediated by yeast heat shock transcription factor. Mol Microbiol 2006;60:240–251.
  • Kruegel U, Robison B, Dange T, Kahlert G, Delaney JR, Kotireddy S, et al.. Elevated proteasome capacity extends replicative lifespan in Saccharomyces cerevisiae. PLoS Genet 2011;7:e1002253.
  • Dahlmann B, Rutschmann M, Kuehn L, Reinauer H. Activation of the multicatalytic proteinase from rat skeletal muscle by fatty acids or sodium dodecyl sulphate. Biochem J 1985;228:171–177.
  • Watanabe N, Yamada S. Activation of 20S proteasomes from spinach leaves by fatty acids. Plant Cell Physiol 1996;37: 147–151.
  • Kohler A, Cascio P, Leggett DS, Woo KM, Goldberg AL, Finley D. The axial channel of the proteasome core particle is gated by the Rpt2 ATPase and controls both substrate entry and product release. Mol Cell 2001;7:1143–1152.
  • Kisselev AF, Kaganovich D, Goldberg AL. Binding of hydrophobic peptides to several non-catalytic sites promotes peptide hydrolysis by all active sites of 20 S proteasomes. Evidence for peptide-induced channel opening in the alpha-rings. J Biol Chem 2002;277:22260–22270.
  • Wilk S, Chen WE. Synthetic peptide-based activators of the proteasome. Mol Biol Rep 1997;24:119–124.
  • Matsumura K, Aketa K. Proteasome (multicatalytic proteinase) of sea urchin sperm and its possible participation in the acrosome reaction. Mol Reprod Dev 1991;29:189–199.
  • Ohkubo I, Gasa S, Namikawa C, Makita A, Sasaki M. Human erythrocyte multicatalytic proteinase: activation and binding to sulfated galacto- and lactosylceramides. Biochem Biophys Res Commun 1991;174:1133–1140.
  • Ruiz de Mena I, Mahillo E, Arribas J, Castano JG. Kinetic mechanism of activation by cardiolipin (diphosphatidylglycerol) of the rat liver multicatalytic proteinase. Biochem J 1993;296:93–97.
  • Silva GM, Netto LE, Simões V, Santos LF, Gozzo FC, Demasi MA, et al.. Redox control of 20S proteasome gating. Antioxid Redox Signal 2012;16:1183–1194.
  • Katsiki M, Chondrogianni N, Chinou I, Rivett AJ, Gonos ES. The olive constituent oleuropein exhibits proteasome stimulatory properties in vitro and confers life span extension of human embryonic fibroblasts. Rejuvenation Res 2007; 10:157–172.
  • Bulteau AL, Moreau M, Saunois A, Nizard C, Friguet B. Algae extract-mediated stimulation and protection of proteasome activity within human keratinocytes exposed to UVA and UVB irradiation. Antioxid Redox Signal 2006;8:136–143.
  • Huang L, Ho P, Chen CH. Activation and inhibition of the proteasome by betulinic acid and its derivatives. FEBS Lett 2007;581:4955–4959.
  • Dang Z, Lin A, Ho P, Soroka D, Lee KH, Huang L, Chen CH. Synthesis and proteasome inhibition of lithocholic acid derivatives. Bioorg Med Chem Lett 2011; 21:1926–1928.
  • Kwak MK, Wakabayashi N, Greenlaw JL, Yamamoto M, Kensler TW. Antioxidants enhance mammalian proteasome expression through the Keap1-Nrf2 signaling pathway. Mol Cell Biol 2003;23:8786–8794.
  • Lewis KN, Mele J, Hayes JD, Buffenstein R. Nrf2, a guardian of healthspan and gatekeeper of species longevity. Integr Comp Biol 2010;50:829–843.
  • Nguyen T, Yang CS, Pickett CB. The pathways and molecular mechanisms regulating Nrf2 activation in response to chemical stress. Free Radic Biol Med 2004;37:433–441.
  • Wasserman WW, Fahl WE. Functional antioxidant responsive elements. Proc Natl Acad Sci USA 1997;94: 5361–5366.
  • D’Autréaux B, Toledano MB. ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 2007;8:813–824.
  • Furukawa M, Xiong Y. BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase. Mol Cell Biol 2005;25:162–171.
  • Boutten A, Goven D, Artaud-Macari E, Boczkowski J, Bonay M. NRF2 targeting: a promising therapeutic strategy in chronic obstructive pulmonary disease. Trends Mol Med 2011;17:363–371.
  • Surh YJ, Kundu JK, Na HK. Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals. Planta Med 2008;74:1526–1539.
  • Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, et al.. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 1997;236:313–322.
  • Venugopal R, Jaiswal AK. Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes. Oncogene 1998;17:3145–3156.
  • Eggler AL, Gay KA, Mesecar AD. Molecular mechanisms of natural products in chemoprevention: induction of cytoprotective enzymes by Nrf2. Mol Nutr Food Res 2008;52: S84–S94.
  • Lau A, Villeneuve NF, Sun Z, Wong PK, Zhang DD. Dual roles of Nrf2 in cancer. Pharmacol Res 2008;58:262–270.
  • Kapeta S, Chondrogianni N, Gonos ES. Nuclear erythroid factor 2-mediated proteasome activation delays senescence in human fibroblasts. J Biol Chem 2010;285:8171–8184.
  • Chondrogianni N, Kapeta S, Chinou I, Vassilatou K, Papassideri I, Gonos ES. Anti-ageing and rejuvenating effects of quercetin. Exp Gerontol 2010;45:763–771.
  • Tanigawa S, Fujii M, Hou DX. Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin. Free Radic Biol Med 2007;42:1690–1703.
  • Kampkotter A, Timpel C, Zurawski RF, Ruhl S, Chovolou Y, Proksch P, Watjen W. Increase of stress resistance and lifespan of Caenorhabditis elegans by quercetin. Comp Biochem Physiol B Biochem Mol Biol 2008;149:314–323.
  • Pietsch K, Saul N, Menzel R, Stürzenbaum SR, Steinberg CE. Quercetin mediated lifespan extension in Caenorhabditis elegans is modulated by age-1, daf-2, sek-1 and unc-43. Biogerontology 2009;10:565–578.
  • Ishii T, Itoh K, Ruiz E, Leake DS, Unoki H, Yamamoto M, Mann GE. Role of Nrf2 in the regulation of CD36 and stress protein expression in murine macrophages: activation by oxidatively modified LDL and 4-hydroxynonenal. Circ Res 2004;94:609–616.
  • Reiser K, McCormick RJ, Rucker RB. Enzymatic and nonenzymatic cross-linking of collagen and elastin. FASEB J 1992;6:2439–2449.
  • Rees MD, Kennett EC, Whitelock JM, Davies MJ. Oxidative damage to extracellular matrix and its role in human pathologies. Free Radic Biol Med 2008;44:1973–2001.
  • Kuzuya M, Asai T, Kanda S, Maeda K, Cheng XW, Iguchi A. Glycation cross-links inhibit matrix metalloproteinase-2 activation in vascular smooth muscle cells cultured on collagen lattice. Diabetologia 2001;44:433–436.
  • Chellan P, Nagaraj RH. Protein crosslinking by the Maillard reaction: dicarbonyl-derived imidazolium crosslinks in aging and diabetes. Arch Biochem Biophys 1999;368:98–104.
  • Sell DR, Biemel KM, Reihl O, Lederer MO, Strauch CM, Monnier VM. Glucosepane is a major protein cross-link of the senescent human extracellular matrix. Relationship with diabetes. J Biol Chem 2005;280:12310–12315.
  • Biemel KM, Friedl DA, Lederer MO. Identification and quantification of major maillard cross-links in human serum albumin and lens protein. Evidence for glucosepane as the dominant compound. J Biol Chem 2002;277:24907–24915.
  • Nasiri R, Field MJ, Zahedi M, Moosavi-Movahedi AA. Cross-linking mechanisms of arginine and lysine with α,β-dicarbonyl compounds in aqueous solution. J Phys Chem A 2011;115:13542–13555.
  • Vasan S, Zhang X, Zhang X, Kapurniotu A, Bernhagen J, Teichberg S, et al.. An agent cleaving glucose-derived protein crosslinks in vitro and in vivo. Nature 1996;382:275–278.
  • Thornalley PJ, Minhas HS. Rapid hydrolysis and slow alpha,beta-dicarbonyl cleavage of an agent proposed to cleave glucose-derived protein cross-links. Biochem Pharmacol 1999;57:303–307.
  • Wolffenbuttel BH, Boulanger CM, Crijns FR, Huijberts MS, Poitevin P, Swennen GN, et al.. Breakers of advanced glycation end products restore large artery properties in experimental diabetes. Proc Natl Acad Sci USA 1998;95:4630–4634.
  • Cheng G, Wang LL, Qu WS, Long L, Cui H, Liu HY, et al.. C16, a novel advanced glycation endproduct breaker, restores cardiovascular dysfunction in experimental diabetic rats. Acta Pharmacol Sin 2005;26:1460–1466.
  • Cheng G, Wang LL, Long L, Liu HY, Cui H, Qu WS, Li S. Beneficial effects of C36, a novel breaker of advanced glycation endproducts cross-links, on the cardiovascular system of diabetic rats. Br J Pharmacol 2007;152:1196–1206.
  • Joshi D, Gupta R, Dubey A, Shiwalkar A, Pathak P, Gupta RC, et al.. TRC4186, a novel AGE-breaker, improves diabetic cardiomyopathy and nephropathy in Ob-ZSF1 model of type 2 diabetes. J Cardiovasc Pharmacol 2009;54:72–81.
  • Chandra KP, Shiwalkar A, Kotecha J, Thakkar P, Srivastava A, Chauthaiwale V, et al.. Phase I clinical studies of the advanced glycation end-product (AGE)-breaker TRC4186: safety, tolerability and pharmacokinetics in healthy subjects. Clin Drug Investig 2009;29:559–575.
  • Nagai R, Murray DB, Metz TO, Baynes JW. Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications. Diabetes 2012;61:549–559.
  • Yang S, Litchfield JE BJ. AGE-breakers cleave model compounds, but do not break Maillard crosslinks in skin and tail collagen from diabetic rats. Arch Biochem Biophys 2003;412:42–46.
  • Mentink CJ, Hendriks M, Levels AA, Wolffenbuttel BH. Glucose-mediated cross-linking of collagen in rat tendon and skin. Clin Chim Acta 2002;321:69–76.
  • Price DL, Rhett PM, Thorpe SR, Baynes JW. Chelating activity of advanced glycation end-product inhibitors. J Biol Chem 2001;276:48967–48972.
  • Rahbar S, Figarola JL. Novel inhibitors of advanced glycation endproducts. Arch Biochem Biophys 2003;419:63–79.
  • Kim T, Spiegel DA. The unique reactivity of N-phenacyl-derived thiazolium salts toward alpha-dicarbonyl compounds. Rejuvenation Res 2013;16:43–50.
  • Li YM, Tan AX, Vlassara H. Antibacterial activity of lysozyme and lactoferrin is inhibited by binding of advanced glycation-modified proteins to a conserved motif. Nat Med 1995;1:1057–1061.
  • Zheng F, Cai W, Mitsuhashi T, Vlassara H. Lysozyme enhances renal excretion of advanced glycation endproducts in vivo and suppresses adverse age-mediated cellular effects in vitro: a potential AGE sequestration therapy for diabetic nephropathy?Mol Med 2001;7:737–747.
  • Mitsuhashi T, Li YM, Fishbane S, Vlassara H. Depletion of reactive advanced glycation endproducts from diabetic uremic sera using a lysozyme-linked matrix. J Clin Invest 1997;100:847–854.
  • Cocchietto M, Zorzin L, Toffoli B, Candido R, Fabris B, Stebel M, Sava G. Orally administered microencapsulated lysozyme downregulates serum AGE and reduces the severity of early-stage diabetic nephropathy. Diabetes Metab 2008;34:587–594.
  • Liu H, Zheng F, Cao Q, Ren B, Zhu L, Striker G, Vlassara H. Amelioration of oxidant stress by the defensin lysozyme. Am J Physiol Endocrinol Metab 2006;290: E824–E832.
  • Liu H, Zheng F, Li Z, Uribarri J, Ren B, Hutter R, et al.. Reduced acute vascular injury and atherosclerosis in hyperlipidemic mice transgenic for lysozyme. Am J Pathol 2006;169:303–313.
  • Pettersson C, Karlsson H, Ståhlman M, Larsson T, Fagerberg B, Lindahl M, et al.. LDL-associated apolipoprotein J and lysozyme are associated with atherogenic properties of LDL found in type 2 diabetes and the metabolic syndrome. J Intern Med 2011;269:306–321.
  • Ueda S, Yamagishi S, Takeuchi M, Kohno K, Shibata R, Matsumoto Y, et al.. Oral adsorbent AST-120 decreases serum levels of AGEs in patients with chronic renal failure. Mol Med 2006;12:180–184.
  • Yamagishi S, Nakamura K, Matsui T, Inoue H, Takeuchi M. Oral administration of AST-120 (Kremezin) is a promising therapeutic strategy for advanced glycation end product (AGE)-related disorders. Med Hypotheses 2007;69: 666–668.
  • Nakamura T, Sato E, Fujiwara N, Kawagoe Y, Suzuki T, Ueda Y, Yamagishi S. Oral adsorbent AST-120 ameliorates tubular injury in chronic renal failure patients by reducing proteinuria and oxidative stress generation. Metabolism 2011;60:260–264.
  • Hayashino Y, Fukuhara S, Akizawa T, Asano Y, Wakita T, Onishi Y, Kurokawa K. CAP-KD study group.Cost-effectiveness of administering oral adsorbent AST-120 to patients with diabetes and advance-stage chronic kidney disease. Diabetes Res Clin Pract 2010;90:154–159.
  • Maeda K, Hamada C, Hayashi T, Shou I, Wakabayashi M, Fukui M, et al.. Long-term effects of the oral adsorbent, AST-120, in patients with chronic renal failure. J Int Med Res 2009;37:205–213.
  • Uribarri J, Woodruff S, Goodman S, Cai W, Chen X, Pyzik R, et al.. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc 2010;110:911–916.
  • Sgarbieri VC, Amaya J, Tanaka M, Chichester CO. Nutritional consequences of the Maillard reaction. Amino acid availability from fructose-leucine and fructose-tryptophan in the rat. J Nutr 1973;103:657–663.
  • Koschinsky T, He CJ, Mitsuhashi T, Bucala R, Liu C, Buenting C, et al.. Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor in diabetic nephropathy. Proc Natl Acad Sci USA 1997;94: 6474–6479.
  • Huebschmann AG, Regensteiner JG, Vlassara H, Reusch JE. Diabetes and advanced glycoxidation end products. Diabetes Care 2006;29:1420–1432.
  • Zheng F, He C, Li J, Vlassara H. Restriction of AGE content of food without lowering protein intake prevents diabetic nephropathy in mice. Diabetes 2000;49:A161.
  • Vlassara H, Fuh H, Makita Z, Krungkai S, Cerami A, Bucala R. Exogenous advanced glycosylation end products induce complex vascular dysfunction in normal animals: a model for diabetic and aging complications. Proc Natl Acad Sci USA 1992;89:12043–12047.
  • Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 2006;114:597–605.
  • Goh SY, Cooper ME. Clinical review: the role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab 2008;93:1143–1152.
  • Yamagishi S. Role of advanced glycation end products (AGEs) and receptor for AGEs (RAGE) in vascular damage in diabetes. Exp Gerontol 2011;46:217–224.
  • Ramasamy R, Vannucci SJ, Yan SS, Herold K, Yan SF, Schmidt AM. Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. Glycobiology 2005;15:16R–28R.
  • Ramasamy R, Yan SF, Schmidt AM. The diverse ligand repertoire of the receptor for advanced glycation endproducts and pathways to the complications of diabetes. Vascul Pharmacol 2012;57:160–167.
  • Stogsdill JA, Stogsdill MP, Porter JL, Hancock JM, Robinson AB, Reynolds PR. Embryonic overexpression of receptors for advanced glycation end-products by alveolar epithelium induces an imbalance between proliferation and apoptosis. Am J Respir Cell Mol Biol 2012;47:60–66.
  • Sakatani S, Yamada K, Homma C, Munesue S, Yamamoto Y, Yamamoto H, Hirase H. Deletion of RAGE causes hyperactivity and increased sensitivity to auditory stimuli in mice. PLoS One 2009;4:e8309.
  • Sorci G, Riuzzi F, Giambanco I, Donato R. RAGE in tissue homeostasis, repair and regeneration. Biochim Biophys Acta 2013;1833:101–109.
  • Han YT, Choi GI, Son D, Kim NJ, Yun H, Lee S, et al.. Ligand-based design, synthesis, and biological evaluation of 2-aminopyrimidines, a novel series of receptor for advanced glycation end products (RAGE) inhibitors. J Med Chem 2012;55:9120–9135.
  • Sparvero LJ, Asafu-Adjei D, Kang R, Tang D, Amin N, Im J, et al.. RAGE (Receptor for Advanced Glycation Endproducts), RAGE ligands, and their role in cancer and inflammation. J Transl Med 2009;7:17.
  • Barlovic DP, Soro-Paavonen A, Jandeleit-Dahm KA. RAGE biology, atherosclerosis and diabetes. Clin Sci (Lond) 2011;121:43–55.
  • Yamamoto Y, Kato I, Doi T, Yonekura H, Ohashi S, Takeuchi M, et al.. Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice. J Clin Invest 2001;108:261–268.
  • Chen CY, Abell AM, Moon YS, Kim KH. An advanced glycation end product (AGE)-receptor for AGEs (RAGE) axis restores adipogenic potential of senescent preadipocytes through modulation of p53 protein function. J Biol Chem 2012;287:44498–44507.
  • Fritz G. RAGE: a single receptor fits multiple ligands. Trends Biochem Sci 2011;36:625–632.
  • Xue J, Rai V, Singer D, Chabierski S, Xie J, Reverdatto S, et al.. Advanced glycation end product recognition by the receptor for AGEs. Structure 2011;19:722–732.
  • Schalkwijk CG, Miyata T. Early- and advanced non- enzymatic glycation in diabetic vascular complications: the search for therapeutics. Amino Acids 2012;42:1193–1204.
  • Touré F, Fritz G, Li Q, Rai V, Daffu G, Zou YS, et al.. Formin mDia1 mediates vascular remodeling via integration of oxidative and signal transduction pathways. Circ Res 2012;110:1279–1293.
  • Shang L, Ananthakrishnan R, Li Q, Quadri N, Abdillahi M, Zhu Z, et al.. RAGE modulates hypoxia/reoxygenation injury in adult murine cardiomyocytes via JNK and GSK-3beta signaling pathways. PLoS One 2010;5:e10092.
  • Kumano-Kuramochi M, Ohnishi-Kameyama M, Xie Q, Niimi S, Kubota F, Komba S, Machida S. Minimum stable structure of the receptor for advanced glycation end product possesses multi ligand binding ability. Biochem Biophys Res Commun 2009;386:130–134.
  • Basta G. Receptor for advanced glycation endproducts and atherosclerosis: From basic mechanisms to clinical implications. Atherosclerosis 2008;196:9–21.
  • Jiao L, Chen L, Alsarraj A, Ramsey D, Duan Z, El-Serag HB. Plasma soluble receptor for advanced glycation end-products and risk of colorectal adenoma. Int J Mol Epidemiol Genet 2012;3:294–304.
  • Falcone C, Emanuele E, D’Angelo A, Buzzi MP, Belvito C, Cuccia M, Geroldi D. Plasma levels of soluble receptor for advanced glycation end products and coronary artery disease in nondiabetic men. Arterioscler Thromb Vasc Biol 2005;25:1032–1037.
  • Katakami N, Matsuhisa M, Kaneto H, Matsuoka TA, Sakamoto K, Nakatani Y, et al.. Decreased endogenous secretory advanced glycation end product receptor in type 1 diabetic patients: its possible association with diabetic vascular complications. Diabetes Care 2005;28:2716–2721.
  • Koyama H, Shoji T, Fukumoto S, Shinohara K, Shoji T, Emoto M, et al.. Low circulating endogenous secretory receptor for AGEs predicts cardiovascular mortality in patients with end-stage renal disease. Arterioscler Thromb Vasc Biol 2007;27:147–153.
  • Nakamura K, Yamagishi S, Adachi H, Kurita-Nakamura Y, Matsui T, Yoshida T, et al.. Elevation of soluble form of receptor for advanced glycation end products (sRAGE) in diabetic subjects with coronary artery disease. Diabetes Metab Res Rev 2007;23:368–371.
  • Yang SJ, Kim S, Hwang SY, Kim TN, Choi HY, Yoo HJ, et al.. Association between sRAGE, esRAGE levels and vascular inflammation: analysis with (18)F-fluorodeoxyglucose positron emission tomography. Atherosclerosis 2012; 220:402–406.
  • Qian L, Ding L, Cheng L, Zhu X, Zhao H, Jin J, et al.. Early biomarkers for post-stroke cognitive impairment. J Neurol 2012;259:2111–2118.
  • Wittkowski H, Hirono K, Ichida F, Vogl T, Ye F, Yanlin X, et al.. Acute Kawasaki disease is associated with reverse regulation of soluble receptor for advance glycation end products and its proinflammatory ligand S100A12. Arthritis Rheum 2007;56:4174–4181.
  • Greco R, Amantea D, Mangione AS, Petrelli F, Gentile R, Nappi G, et al.. Modulation of RAGE isoforms expression in the brain and plasma of rats exposed to transient focal cerebral ischemia. Neurochem Res 2012;1508–1516.
  • Liang F, Jia J, Wang S, Qin W, Liu G. Decreased plasma levels of soluble low density lipoprotein receptor-related protein-1 (sLRP) and the soluble form of the receptor for advanced glycation end products (sRAGE) in the clinical diagnosis of Alzheimer's disease. J Clin Neurosci 2012;[Epub ahead of print].
  • Marsche G, Weigle B, Sattler W, Malle E. Soluble RAGE blocks scavenger receptor CD36-mediated uptake of hypochlorite-modified low-density lipoprotein. FASEB J 2007;21:3075–3082.
  • Kotani K, Caccavello R, Taniguchi N, Gugliucci A. Circulating soluble receptor for advanced glycation end products is inversely correlated to oxidized low-density lipoproteins in asymptomatic subjects. J Int Med Res 2012;40:1878–1883.
  • Rai V, Touré F, Chitayat S, Pei R, Song F, Li Q, et al.. Lysophosphatidic acid targets vascular and oncogenic pathways via RAGE signaling. J Exp Med 2012;209:2339–2350.
  • Lanati N, Emanuele E, Brondino N, Geroldi D. Soluble RAGE-modulating drugs: state-of-the-art and future perspectives for targeting vascular inflammation. Curr Vasc Pharmacol 2010;8:86–92.
  • Basta G, Navarra T, De Simone P, Del Turco S, Gastaldelli A, Filipponi F. What is the role of the receptor for advanced glycation end products-ligand axis in liver injury?Liver Transpl 2011;17:633–640.
  • Wendt TM, Tanji N, Guo J, Kislinger TR, Qu W, Lu Y, et al.. RAGE drives the development of glomerulosclerosis and implicates podocyte activation in the pathogenesis of diabetic nephropathy. Am J Pathol 2003;162:1123–1137.
  • Chen Y, Yan SS, Colgan J, Zhang HP, Luban J, Schmidt AM, et al.. Blockade of late stages of autoimmune diabetes by inhibition of the receptor for advanced glycation end products. J Immunol 2004;173:1399–1405.
  • Deane R, Singh I, Sagare AP, Bell RD, Ross NT, LaRue B, et al.. A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease. J Clin Invest 2012;122:1377–1392.
  • Zlokovic BV. New therapeutic targets in the neurovascular pathway in Alzheimer's disease. Neurotherapeutics 2008; 5:409–414.
  • Sabbagh MN, Agro A, Bell J, Aisen PS, Schweizer E, Galasko D. PF-04494700, an oral inhibitor of receptor for advanced glycation end products (RAGE), in Alzheimer's disease. Alzheimer Dis Assoc Disord 2011;25:206–212.
  • Feng L, Xu YH, Wang SS, Au-Yeung W, Zheng ZG, Zhu Q, Xiang P. Competitive binding between 4,4’-diphenylmethane- bis(methyl) carbamate and RAGE ligand MG-H1 on human umbilical vein endothelial cell by cell membrane chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 2012;881–882:55–62.
  • Jung DH, Kim YS, Kim JS. Screening system of blocking agents of the receptor for advanced glycation endproducts in cells using fluorescence. Biol Pharm Bull 2012;35: 1826–1830.
  • Win MT, Yamamoto Y, Munesue S, Saito H, Han D, Motoyoshi S, et al.. Regulation of RAGE for attenuating progression of diabetic vascular complications. Exp Diabetes Res 2012;2012:894605.
  • Gospodarska E, Kupniewska-Kozak A, Goch G, Dadlez M. Binding studies of truncated variants of the Aβ peptide to the V-domain of the RAGE receptor reveal Aβ residues responsible for binding. Biochim Biophys Acta 2011;1814:592–609.
  • Hearst SM, Walker LR, Shao Q, Lopez M, Raucher D, Vig PJ. The design and delivery of a thermally responsive peptide to inhibit S100B-mediated neurodegeneration. Neuroscience 2011;197:369–380.
  • Arumugam T, Ramachandran V, Gomez SB, Schmidt AM, Logsdon CD. S100P-derived RAGE antagonistic peptide reduces tumor growth and metastasis. Clin Cancer Res 2012;18:4356–4364.
  • Rao NV, Argyle B, Xu X, Reynolds PR, Walenga JM, Prechel M, et al.. Low anticoagulant heparin targets multiple sites of inflammation, suppresses heparin-induced thrombocytopenia, and inhibits interaction of RAGE with its ligands. Am J Physiol Cell Physiol 2010;299:C97–C110.
  • Bansal S, Siddarth M, Chawla D, Banerjee BD, Madhu SV, Tripathi AK. Advanced glycation end products enhance reactive oxygen and nitrogen species generation in neutrophils in vitro. Mol Cell Biochem 2012;361:289–296.
  • Zhao LM, Zhang W, Wang LP, Li GR, Deng XL. Advanced glycation end products promote proliferation of cardiac fibroblasts by upregulation of K(Ca)3.1 channels. Pflugers Arch 2012;464:613–621.
  • Cheng CL, Tang Y, Zheng Z, Liu X, Ye ZC, Wang C, Lou TQ. Advanced glycation end-products activate the renin-angiotensin system through the RAGE/PI3-K signaling pathway in podocytes. Clin Invest Med 2012;35:E282.
  • Mizumoto S, Takahashi J, Sugahara K. Receptor for advanced glycation end products (RAGE) functions as receptor for specific sulfated glycosaminoglycans, and anti-RAGE antibody or sulfated glycosaminoglycans delivered in vivo inhibit pulmonary metastasis of tumor cells. J Biol Chem 2012; 287:18985–18994.
  • Clynes R, Herold K, Schmidt AM. RAGE: exacting a toll on the host in response to polymicrobial sepsis and Listeria monocytogenes. Crit Care 2007;11:183.
  • Webster SJ, Mruthinti S, Hill WD, Buccafusco JJ, Terry AVJ. An aqueous orally active vaccine targeted against a RAGE/AB complex as a novel therapeutic for Alzheimer's disease. Neuromolecular Med 2012;14:119–130.
  • Zhang Q, O’Hearn S, Kavalukas SL, Barbul A. Role of high mobility group box 1 (HMGB1) in wound healing. J Surg Res 2012;176:343–347.
  • Vugmeyster Y, DeFranco D, Pittman DD, Xu X. Pharmacokinetics and lung distribution of a humanized anti-RAGE antibody in wild-type and RAGE-/- mice. MAbs 2010;2:571–575.
  • Christaki E, Opal SM, Keith JCJ, Kessimian N, Palardy JE, Parejo NA, et al.. A monoclonal antibody against RAGE alters gene expression and is protective in experimental models of sepsis and pneumococcal pneumonia. Shock 2011;35:492–498.
  • Müller-Krebs S, Kihm LP, Madhusudhan T, Isermann B, Reiser J, Zeier M, Schwenger V. Human RAGE antibody protects against AGE-mediated podocyte dysfunction. Nephrol Dial Transplant 2012;27:3129–3136.
  • Li F, Cai Z, Chen F, Shi X, Zhang Q, Chen S, et al.. Pioglitazone attenuates progression of aortic valve calcification via down-regulating receptor for advanced glycation end products. Basic Res Cardiol 2012;107:306.
  • Yamagishi S, Nakamura K, Matsui T. Regulation of advanced glycation end product (AGE)-receptor (RAGE) system by PPAR-gamma agonists and its implication in cardiovascular disease. Pharmacol Res 2009;60:174–178.
  • Marx N, Walcher D, Ivanova N, Rautzenberg K, Jung A, Friedl R, et al.. Thiazolidinediones reduce endothelial expression of receptors for advanced glycation end products. Diabetes 2004;53:2662–2668.
  • Liu X, Luo D, Zheng M, Hao Y, Hou L, Zhang S. Effect of pioglitazone on insulin resistance in fructose-drinking rats correlates with AGEs/RAGE inhibition and block of NADPH oxidase and NF kappa B activation. Eur J Pharmacol 2010;629:153–158.
  • Wang K, Zhou Z, Zhang M, Fan L, Forudi F, Zhou X, et al.. Peroxisome proliferator-activated receptor gamma down-regulates receptor for advanced glycation end products and inhibits smooth muscle cell proliferation in a diabetic and nondiabetic rat carotid artery injury model. J Pharmacol Exp Ther 2006;317:37–43.
  • Matsui T, Yamagishi S, Takeuchi M, Ueda S, Fukami K, Okuda S. Nifedipine inhibits advanced glycation end products (AGEs) and their receptor (RAGE) interaction-mediated proximal tubular cell injury via peroxisome proliferator- activated receptor-gamma activation. Biochem Biophys Res Commun 2010;398:326–330.
  • Ishibashi Y, Matsui T, Takeuchi M, Yamagishi S. Metformin inhibits advanced glycation end products (AGEs)-induced renal tubular cell injury by suppressing reactive oxygen species generation via reducing receptor for AGEs (RAGE) expression. Horm Metab Res 2012;44:891–895.
  • Matsui T, Yamagishi S, Takeuchi M, Ueda S, Fukami K, Okuda S. Irbesartan inhibits advanced glycation end product (AGE)-induced proximal tubular cell injury in vitro by suppressing receptor for AGEs (RAGE) expression. Pharmacol Res 2010;61:34–39.
  • Ishibashi Y, Matsui T, Takeuchi M, Yamagishi S. Beneficial effects of metformin and irbesartan on advanced glycation end products (AGEs)-RAGE-induced proximal tubular cell injury. Pharmacol Res 2012;65:297–302.
  • Yamagishi S, Matsui T, Nakamura K, Takeuchi M, Inoue H. Telmisartan inhibits advanced glycation end products (AGEs)-elicited endothelial cell injury by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-gammaactivation. Protein Pept Lett 2008;15:850–853.
  • Yamagishi S, Matsui T, Nakamura K, Inoue H, Takeuchi M, Ueda S, et al.. Olmesartan blocks advanced glycation end products (AGEs)-induced angiogenesis in vitro by suppressing receptor for AGEs (RAGE) expression. Microvasc Res 2008;75:130–134.
  • Ishibashi Y, Matsui T, Takeuchi M, Yamagishi S. Vardenafil, an inhibitor of phosphodiesterase-5, blocks advanced glycation end product (AGE)-induced up-regulation of monocyte chemoattractant protein-1 mRNA levels in endothelial cells by suppressing AGE receptor (RAGE) expression via elevation of cGMP. Clin Exp Med 2011;11:131–135.
  • Ishibashi Y, Matsui T, Takeuchi M, Yamagishi S. Glucagon-like peptide-1 (GLP-1) inhibits advanced glycation end product (AGE)-induced up-regulation of VCAM-1 mRNA levels in endothelial cells by suppressing AGE receptor (RAGE) expression. Biochem Biophys Res Commun 2010;391:1405–1408.
  • Ishibashi Y, Matsui T, Ohta K, Tanoue R, Takeuchi M, Asanuma K, et al.. PEDF inhibits AGE-induced podocyte apoptosis via PPAR-gamma activation. Microvasc Res 2013;85:54–58.
  • Ishibashi Y, Yamagishi S, Matsui T, Ohta K, Tanoue R, Takeuchi M, et al.. Pravastatin inhibits advanced glycation end products (AGEs)-induced proximal tubular cell apoptosis and injury by reducing receptor for AGEs (RAGE) level. Metabolism 2012;61:1067–1072.
  • Wu J, Zhao MY, Zheng H, Zhang H, Jiang Y. Pentoxifylline alleviates high-fat diet-induced non-alcoholic steatohepatitis and early atherosclerosis in rats by inhibiting AGE and RAGE expression. Acta Pharmacol Sin 2010;31:1367–1375.
  • Jing YH, Chen KH, Yang SH, Kuo PC, Chen JK. Resveratrol ameliorates vasculopathy in STZ-induced diabetic rats: role of AGE-RAGE signalling. Diabetes Metab Res Rev 2010;26:212–222.
  • Yu W, Wu J, Cai F, Xiang J, Zha W, Fan D, et al.. Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats. PLoS One 2012;7:e52013.
  • Li JZ, Wu JH, Yu SY, Shao QR, Dong XM. Inhibitory effects of paeoniflorin on lysophosphatidylcholine-induced inflammatory factor production in human umbilical vein endothelial cells. Int J Mol Med 2013;31:493–497.
  • Chen F, Zhang HQ, Zhu J, Liu KY, Cheng H, Li GL, et al.. Puerarin enhances superoxide dismutase activity and inhibits RAGE and VEGF expression in retinas of STZ-induced early diabetic rats. Asian Pac J Trop Med 2012;5:891–896.
  • Liu R, Wu CX, Zhou D, Yang F, Tian S, Zhang L, et al.. Pinocembrin protects against β-amyloid-induced toxicity in neurons through inhibiting receptor for advanced glycation end products (RAGE)-independent signaling pathways and regulating mitochondrion-mediated apoptosis. BMC Med 2012;10:105.
  • Xiang M, Wang J, Zhang Y, Ling J, Xu X. Attenuation of aortic injury by ursolic acid through RAGE-Nox-NFκB pathway in streptozocin-induced diabetic rats. Arch Pharm Res 2012;35:877–886.
  • Lee SH, Kim YS, Lee SJ, Lee BC. The protective effect of Salvia miltiorrhiza in an animal model of early experimentally induced diabetic nephropathy. J Ethnopharmacol 2011;137:1409–1414.
  • Peng CH, Chyau CC, Chan KC, Chan TH, Wang CJ, Huang CN. Hibiscus sabdariffa polyphenolic extract inhibits hyperglycemia, hyperlipidemia, and glycation-oxidative stress while improving insulin resistance. J Agric Food Chem 2011;59:9901–9909.
  • Xu L, Li B, Cheng M, Zhang W, Pan J, Zhang C, Gao H. Oral administration of grape seed proanthocyanidin extracts downregulate RAGE dependant nuclear factor- kappa BP65 expression in the hippocampus of streptozotocin induced diabetic rats. Exp Clin Endocrinol Diabetes 2008;116: 215–224.
  • Sakuraoka Y, Sawada T, Okada T, Shiraki T, Miura Y, Hiraishi K, et al.. MK615 decreases RAGE expression and inhibits TAGE-induced proliferation in hepatocellular carcinoma cells. World J Gastroenterol 2010;16:5334–5341.
  • Song MK, Salam NK, Roufogalis BD, Huang TH. Lycium barbarum (Goji Berry) extracts and its taurine component inhibit PPAR-γ-dependent gene transcription in human retinal pigment epithelial cells: Possible implications for diabetic retinopathy treatment. Biochem Pharmacol 2011; 82:1209–1218.
  • Yan FL, Zheng Y, Zhao FD. Effects of Ginkgo biloba extract EGb761 on expression of RAGE and LRP-1 in cerebral microvascular endothelial cells under chronic hypoxia and hypoglycemia. Acta Neuropathol 2008;116:529–535.
  • Baek GH, Jang YS, Jeong SI, Cha J, Joo M, Shin SW, et al.. Rehmannia glutinosa suppresses inflammatory responses elicited by advanced glycation end products. Inflammation 2012;35:1232–1241.
  • de Bittencourt Pasquali MA, Gelain DP, Zeidán-Chuliá F, Pires AS, Gasparotto J, Terra SR, Moreira JC. Vitamin A (retinol) downregulates the receptor for advanced glycation endproducts (RAGE) by oxidant-dependent activation of p38 MAPK and NF-kB in human lung cancer A549 cells. Cell Signal 2013;25:939–954.
  • Pillai SS, Sugathan JK, Indira M. Selenium downregulates RAGE and NFκB expression in diabetic rats. Biol Trace Elem Res 2012;149:71–77.
  • Wei W, Chen M, Zhu Y, Wang J, Zhu P, Li Y, Li J. Down-regulation of vascular HMGB1 and RAGE expression by n-3 polyunsaturated fatty acids is accompanied by amelioration of chronic vasculopathy of small bowel allografts. J Nutr Biochem 2012;23:1333–1340.
  • Chen SA, Chen HM, Yao YD, Hung CF, Tu CS, Liang YJ. Topical treatment with anti-oxidants and Au nanoparticles promote healing of diabetic wound through receptor for advance glycation end-products. Eur J Pharm Sci 2012;47:875–883.
  • González I, Romero J, Rodríguez BL, Pérez-Castro R, Rojas A. The immunobiology of the receptor of advanced glycation end-products: Trends and challenges. Immunobiology 2012;Epub ahead of print.
  • Basta G, Schmidt AM, De Caterina R. Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardiovasc Res 2004; 63:582–592.
  • Baumann M. Role of advanced glycation end products in hypertension and cardiovascular risk: human studies. J Am Soc Hypertens 2012;6:427–435.
  • Basta G, Lazzerini G, Massaro M, Simoncini T, Tanganelli P, Fu C, et al.. Advanced glycation end products activate endothelium through signal-transduction receptor RAGE: a mechanism for amplification of inflammatory responses. Circulation 2002;105:816–822.
  • Farmer DG, Kennedy S. RAGE, vascular tone and vascular disease. Pharmacol Ther 2009;124:185–194.
  • Sakaguchi M, Murata H, Yamamoto K, Ono T, Sakaguchi Y, Motoyama A, et al.. TIRAP, an adaptor protein for TLR2/4, transduces a signal from RAGE phosphorylated upon ligand binding. PLoS One 2011;6:e23132.
  • Fukami K, Ueda S, Yamagishi S, Kato S, Inagaki Y, Takeuchi M, et al.. AGEs activate mesangial TGF-beta-Smad signaling via an angiotensin II type I receptor interaction. Kidney Int 2004;66:2137–2147.
  • Xu Y, Toure F, Qu W, Lin L, Song F, Shen X, et al.. Advanced glycation end product (AGE)-receptor for AGE (RAGE) signaling and up-regulation of Egr-1 in hypoxic macrophages. J Biol Chem 2010;285:23233–23240.
  • Hudson BI, Kalea AZ, Del Mar Arriero M, Harja E, Boulanger E, D’Agati V, Schmidt AM. Interaction of the RAGE cytoplasmic domain with diaphanous-1 is required for ligand-stimulated cellular migration through activation of Rac1 and Cdc42. J Biol Chem 2008;283:34457–34468.
  • Soman S, Raju R, Sandhya VK, Advani J, Khan AA, Harsha HC, et al.. A multicellular signal transduction network of AGE/RAGE signaling. J Cell Commun Signal 2012; Epub ahead of print.
  • Matsunaga-Irie S, Maruyama T, Yamamoto Y, Motohashi Y, Hirose H, Shimada A, Murata M, Saruta T. Relation between development of nephropathy and the p22phox C242T and receptor for advanced glycation end product G1704T gene polymorphisms in type 2 diabetic patients. Diabetes Care 2004;27:303–307.
  • Wautier MP, Chappey O, Corda S, Stern DM, Schmidt AM, Wautier JL. Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. Am J Physiol Endocrinol Metab 2001;280:E685–E694.
  • Yin QQ, Dong CF, Dong SQ, Dong XL, Hong Y, Hou XY, et al.. AGEs induce cell death via oxidative and endoplasmic reticulum stresses in both human SH-SY5Y neuroblastoma cells and rat cortical neurons. Neurobiol Aging 2012;32: 1299–1309.
  • Kim JM, Lee EK, Kim DH, Yu BP, Chung HY. Kaempferol modulates pro-inflammatory NF-kappaB activation by suppressing advanced glycation endproducts-induced NADPH oxidase. Age (Dordr) 2010;32:197–208.
  • Hu P, Lai D, Lu P, Gao J, He H. ERK and Akt signaling pathways are involved in advanced glycation end product-induced autophagy in rat vascular smooth muscle cells. Int J Mol Med 2012;29:613–618.
  • Zhu P, Ren M, Yang C, Hu YX, Ran JM, Yan L. Involvement of RAGE, MAPK and NF-κB pathways in AGEs-induced MMP-9 activation in HaCaT keratinocytes. Exp Dermatol 2012;21:123–129.
  • Bansal S, Siddarth M, Chawla D, Banerjee BD, Madhu SV, Tripathi AK. Advanced glycation end products enhance reactive oxygen and nitrogen species generation in neutrophils in vitro. Mol Cell Biochem 2012;361:289–296.
  • Gill PS, Wilcox CS. NADPH oxidases in the kidney. Antioxid Redox Signal 2006;8:1597–1607.
  • Yan SD, Schmidt AM, Anderson GM, Zhang J, Brett J, Zou YS, et al.. Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins. J Biol Chem 1994;269:9889–9897.
  • Zhang J, Slevin M, Duraisamy Y, Gaffney JA, Smith C, Ahmed N. Comparison of protective effects of aspirin, D-penicillamine and vitamin E against high glucose- mediated toxicity in cultured endothelial cells. Biochim Biophys Acta 2006;1762:551–557.
  • Yamagishi S, Takeuchi M. Nifedipine inhibits gene expression of receptor for advanced glycation end products (RAGE) in endothelial cells by suppressing reactive oxygen species generation. Drugs Exp Clin Res 2004;30:169–175.
  • Yamagishi S, Matsui T, Nakamura K, Inoue H, Takeuchi M, Ueda S, et al.. Olmesartan blocks inflammatory reactions in endothelial cells evoked by advanced glycation end products by suppressing generation of reactive oxygen species. Ophthalmic Res 2008;40:10–15.
  • Marx N, Wöhrle J, Nusser T, Walcher D, Rinker A, Hombach V, et al.. Pioglitazone reduces neointima volume after coronary stent implantation: a randomized, placebo-controlled, double-blind trial in nondiabetic patients. Circulation 2005;112:2792–2798.
  • Liu R, Zhang TT, Zhou D, Bai XY, Zhou WL, Huang C, et al.. Quercetin protects against the Aβ(25–35)-induced amnesic injury: Involvement of inactivation of RAGE-mediated pathway and conservation of the NVU. Neuropharmacology 2012;Dec 8. pii: S0028-3908(0012)00565-00565 [Epub ahead of print].
  • Liu CA, Wang YJ, Na S. Effects soybean isoflavones on RAGE mediated signal transduction in the hippocampus of rats with Alzheimer's disease. Zhongguo Zhong Xi Yi Jie He Za Zhi 2012;32:797–800.
  • Huang JS, Chuang LY, Guh JY, Yang YL, Hsu MS. Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells. Toxicol Appl Pharmacol 2008;233:220–226.
  • Liu R, Zhang TT, Zhou D, Bai XY, Zhou WL, Huang C, et al.. Quercetin protects against the Aβ(25–35)-induced amnesic injury: Involvement of inactivation of RAGE- mediated pathway and conservation of the NVU. Neuropharmacology 2013;67:419–431.
  • Lu J, Wu DM, Zheng YL, Hu B, Zhang ZF, Ye Q, et al.. Ursolic acid attenuates D-galactose-induced inflammatory response in mouse prefrontal cortex through inhibiting AGEs/RAGE/NF-κB pathway activation. Cereb Cortex 2010;20:2540–2548.
  • Golubev A. How could the Gompertz-Makeham law evolve. J Theor Biol 2009;258:1–17.
  • Zarkovic N, Ilic Z, Jurin M, Schaur RJ, Puhl H, Esterbauer H. Stimulation of HeLa cell growth by physiological concentrations of 4-hydroxynonenal. Cell Biochem Funct 1993;11: 279–286.
  • Dwivedi S, Sharma A, Patrick B, Sharma R, Awasthi YC. Role of 4-hydroxynonenal and its metabolites in signaling. Redox Rep 2007;12:4–10.