Free radical generation by early glycation products: a mechanism for accelerated atherogenesis in diabetes.
Non-enzymatic glycation of reactive amino groups in model proteins increased the rate of free radical production at physiologic pH by nearly fifty-fold over non-glycated protein. Superoxide generation was confirmed by electron paramagnetic resonance measurements with the spin-trap phenyl-t-butyl-nitrone. Both Schiff base and Amadori glycation products were found to generate free radicals in a ratio of 1:1.5. Free radicals generated by glycated protein increased peroxidation of membranes of linoleic/arachidonic acid vesicles nearly 2-fold over control, suggesting that the increased glycation of proteins in diabetes may accelerate vascular wall lipid oxidative modification.
Mullarkey
C J
CJ
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
Edelstein
D
D
Brownlee
M
M
D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism*; D002374:Catalase / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003497:Cyclic N-Oxides; D003574:Cytochrome c Group / Q000378:metabolism; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism*; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism; D015227:Lipid Peroxidation; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D009589:Nitrogen Oxides; D012545:Schiff Bases / Q000378:metabolism; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000494:pharmacology
D003497:Cyclic N-Oxides; D003574:Cytochrome c Group; D005609:Free Radicals; D008041:Linoleic Acids; D009589:Nitrogen Oxides; D012545:Schiff Bases; D013113:Spin Labels; D009580:Nitroblue Tetrazolium; C029217:phenyl-N-tert-butylnitrone; D019787:Linoleic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D005947:Glucose