Evidence against nitric oxide-quenching effects of chemically defined Maillard reaction products.
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-epsilon-fructosyllysine or the advanced glycation end product N-epsilon-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 Fe (2+) 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.
Institute of Physiology, Medical Faculty, Technische Universität Dresden, Germany. tlauer@ukaachen.de
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Lauer
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Rassaf
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Planitz
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Preuss
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Krause
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Henle
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Deussen
D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000494:pharmacology; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D015416:Maillard Reaction; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D011485:Protein Binding; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012996:Solutions
D000596:Amino Acids; D017127:Glycation End Products, Advanced; D020030:Nitric Oxide Donors; D012996:Solutions; C033186:fructosyl-lysine; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; C048496:N(6)-carboxymethyllysine; D026423:S-Nitroso-N-Acetylpenicillamine; D004492:Edetic Acid; D008239:Lysine