Free radical generation by early glycation products: A mechanism for accelerated atherogenesis in diabetes

• Published in: Biochemical and biophysical research communications Vol. 173; no. 3; pp. 932 - 939
• Main Authors: Mullarkey, Cathleen J., Edelstein, Diane, Brownlee, Michael
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 31.12.1990; Elsevier
• Subjects: Arteriosclerosis - etiology; Arteriosclerosis - metabolism; Biological and medical sciences; Catalase - pharmacology; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell metabolism, cell oxidation; Cell physiology; Cyclic N-Oxides; Cytochrome c Group - metabolism; Diabetes Complications; Diabetes Mellitus - metabolism; Electron Spin Resonance Spectroscopy; Free Radicals; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; Humans; Hyperglycemia - complications; Hyperglycemia - metabolism; Linoleic Acid; Linoleic Acids - metabolism; Lipid Peroxidation; Molecular and cellular biology; Nitroblue Tetrazolium - metabolism; Nitrogen Oxides; Schiff Bases - metabolism; Spin Labels; Superoxide Dismutase - pharmacology; Human; Proteins; Amine; Diabetes mellitus; EPR spectrometry; Lipids; Glycosylation; Mechanism of action; Atheroma; Free radical
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(05)80875-7

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.