Evidence against Nitric Oxide-quenching Effects of Chemically Defined Maillard Reaction Products

Abstract

Direct interaction between Maillard reaction products (MRPs) and nitric oxide (NO) has been suggested as a pathophysiological mechanism involved in enhanced diabetic arteriosclerosis. Only MRPs without structural characterization have been studied to date. Using chemically synthesized and analytically well defined individual MRPs, we investigated whether the native nitric oxide concentration is directly affected by the Amadori compound N-ε-fructosyllysine or the advanced glycation end product N-ε-carboxymethyllysine. MRPs were incubated with nitric oxide solution or NO donors (SNAP, spermine-NONOate). Changes in the nitrite (oxidative metabolite of NO) concentration served as indicator of NO availability. MRPs, either as free amino acids or covalently bound to bovine serum albumin (BSA), had no influence on nitrite concentration when using NO solution. In contrast, incubation of the respective NO donors with several covalently protein-bound MRPs as well as native BSA significantly reduced nitrite concentration. If SNAP was co-incubated with EDTA or with Fe²⁺ ions, nitrite concentration was decreased or increased, respectively, suggesting a metal ion-dependent alteration of the NO liberation rate. Native NO concentration was not affected by the MRPs tested. Substitution of native NO by NO-releasing substances may be inadequate as a model of NO-MRP interaction, as metal ions or chelators present in compound preparations may affect the NO-liberating mechanism of the donor.

Key words

AGEs - diabetes - nitric oxide - NO donors - endothelial dysfunction

References

• 1 King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections.  Diabetes Care. 1998;  21 1414-1431
• 2 Brownlee M. Biochemistry and molecular cell biology of diabetic complications.  Nature. 2001;  414 813-820
• 3 Marzion D Di, Mohn A, Molini ZH, Giannini C, Chiarelli F. Macroangiopathy in adults and children with diabetes: from molecular mechanisms to vascular damage.  Horm Metab Res. 2006;  38 591-705
• 4 Jensen L, Ostergaard J, Flyvbjerg A. AGE-RAGE and AGE cross-link interaction: important players in the pathogenesis of diabetic kidney disease.  Horm Metab Res. 2004;  37 ((Suppl 1)) 26-34
• 5 Degenhardt TP, Thorpe SR, Baynes JW. Chemical modification of proteins by methylglyoxal.  Cell Mol Biol. 1998;  44 1139-1145
• 6 Wells-Knecht KJ, Zyzak DV, Lichtfield JE, Thorpe SR, Baynes JW. Mechanism of autoxidative glycosylation: identification of glyoxal and arabinose as intermediates in the autoxidative modification of proteins by glucose.  Biochemistry. 1995;  34 3702-3709
• 7 Thornalley PJ. The glyoxalase system: new developments towards functional characterization of a metabolic pathway fundamental to biological life.  Biochem J. 1990;  269 1-11
• 8 Henle T, Miyata T. Advanced glycation end products in uremia.  Adv Ren Replace Ther. 2003;  10 321-331
• 9 Verbeke P, Perichon M, Friguet B, Bakala H. Inhibition of nitric oxide synthase activity by early and advanced glycation end products in cultured rabbit proximal tubular epithelial cells.  Biochem Biophys Acta. 2000;  1502 481-494
• 10 Bucala R, Tracey KJ, Cerami A. Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilatation in experimental diabetes.  J Clin Invest. 1991;  87 432-438
• 11 Glorieux G, Helling R, Henle T, Brunet P, Deppisch R, Lameire N, Vanholder R. In vitro evidence for immune activating effect of specific AGE structures retained in uremia.  Kidney Int. 2004;  66 1873-1880
• 12 Seifert ST, Krause R, Gloe K, Henle T. Metal complexation by the peptide-bound maillard reaction products N(epsilon)-fructoselysine and N(epsilon)-carboxymethyllysine.  J Agric Food Chem. 2004;  52 2347-2350
• 13 Krause R, Knoll K, Henle T. Studies on the formation of furosine and pyridosine during acid hydrolysis of different Amadori products of lysine.  Eur Food Res Technol. 2003;  216 277-283
• 14 Henle T, Klostermeyer H. Determination of protein-bound 2-amino-6-(2-formyl-1-pyrrolyl)-hexanoic acid („pyrraline”) by ion exchange chromatography and photodiode array detection.  Eur Food Res Technol. 1993;  196 1-4
• 15 Foerster A, Henle T. Glycation in food and metaboloic transit of dietary AGEs (advanced glycation end-products): studies on the urinary excretion of pyrraline.  Biochem Soc Trans. 2003;  31 1383-1385
• 16 Kelm M. Nitric oxide metabolism and breakdown.  Biochim Biophys Acta. 1999;  1411 273-289
• 17 Lauer T, Kleinbongard P, Kelm M. Indexes of NO bioavailability in human blood.  News Physiol Sci. 2002;  17 251-255
• 18 Lauer T, Kleinbongard P, Preik M, Rauch BH, Deussen A, Feelisch M, Strauer BE, Kelm M. Direct biochemical evidence for eNOS simulation by bradykinin in the human forearm vasculature.  Basic Res Cardiol. 2003;  98 84-89
• 19 Lauer T, Preik M, Rassaf T, Strauer BE, Deussen A, Feelisch M, Kelm M. Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action.  Proc Natl Acad Sci USA. 2001;  98 12814-12819
• 20 Rassaf T, Preik M, Kleinbongaard P, Lauer T, Heiss C, Strauer BE, Feelisch M, Kelm M. Evidence for in vivo transport of bioactive nitric oxide in human plasma.  J Clin Invest. 2002;  109 1241-1248
• 21 Deussen A, Lloyd HG, Schrader J. Contribution of S-adenosylhomocysteine to cardiac adenosine formation.  J Mol Cell Cardiol. 1989;  21 773-782
• 22 Singh RJ, Hogg N, Joseph J, Kalyanaraman B. Photosensitized decomposition of S-nitrosothiols and 2-methyl-2-nitrosopropane. Possible use for site-directed nitric oxide production.  FEBS Lett. 1995;  360 47-51
• 23 Sexton DJ, Muruganandam A, MacKenney DJ, Mutus B. Visible light photochemical release of nitric oxide from S-nitrosoglutathione: potential photochemotherapeutic applications.  Photochem Photobiol. 1994;  59 ((4)) 463-467
• 24 Feelisch M. The biochemical pathways of nitric oxide formation from nitrovasodilators: Appropriate choice of exogenous NO donors and aspects of preparation and handling of aqueous NO solutions.  J Cardiovasc Pharmacol. 1991;  17 ((Suppl 3)) 25-33
• 25 Singh RJ, Hogg N, Joseph J, Kalyanaraman B. Mechanism of nitric oxide release from S-nitrosothiols.  J Biol Chem. 1996;  271 18596-18603
• 26 Tannenbaum SR. Nitrate and nitrite: origin in humans.  Science. 1979;  205 1333-1337

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