Mechanistic studies of advanced glycosylation end product inhibition by aminoguanidine.
Aminoguanidine-HCl inhibits the formation of advanced glycosylation end products (AGEs) in vitro and in vivo, but the mechanism by which this occurs has not been determined. Aminoguanidine inhibited glucose-derived AGE formation on RNase A by 67-85% at aminoguanidine-glucose molar ratios of 1:5 to 1:50 without affecting the concentration of Amadori products. Fast-atom-bombardment mass spectrometry of RNase peptides incubated with glucose alone or with glucose plus aminoguanidine showed that aminoguanidine inhibited the formation of AGEs without forming an adduct with glycosylated peptide. These data suggest that the primary mechanism of aminoguanidine action is reaction with Amadori-derived fragmentation products in solution. These findings are relevant to the potential clinical use of aminoguanidine in the prevention of diabetic complications.
Edelstein
D
D
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
Brownlee
M
M
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D005947:Glucose / Q000378:metabolism*; D006020:Glycopeptides / Q000302:isolation & purification; D006031:Glycosylation / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D010179:Pancreas / Q000201:enzymology; D012259:Ribonuclease, Pancreatic / Q000378:metabolism*; D016339:Spectrometry, Mass, Fast Atom Bombardment
D006020:Glycopeptides; D006146:Guanidines; D009842:Oligopeptides; D012259:Ribonuclease, Pancreatic; D005947:Glucose; C004479:pimagedine