Nitric oxide and nitroxides can act as efficient scavengers of protein-derived free radicals.
Nitric oxide ((*)NO) may act as either a pro-oxidant or an antioxidant in biological systems. Although (*)NO and nitroxide radicals react slowly with most molecules, they react at near diffusion-controlled rates with other radicals and may therefore be efficient protective agents. This study assessed the ability of (*)NO and nitroxides to intercept specific protein-derived radicals and compared the efficacy of these species. Three protein radical systems were investigated as follows: BSA-derived radicals generated via radical transfer from H(2)O(2)-activated horseradish peroxidase, radicals formed on myoglobin via reaction with H(2)O(2), and carbon-centered radicals formed from amino acid hydroperoxides on exposure to Fe(2+)-EDTA. In each case, radicals were generated in the absence or presence of (*)NO or nitroxides of different size and charge. Concentration-dependent loss of the protein radicals was detected by electron paramagnetic resonance with both (*)NO and nitroxides and time-dependent consumption of (*)NO using an (*)NO electrode. The protein oxidation product dityrosine was significantly reduced by (*)NO and nitroxides, and 3,4-dihydroxyphenylalanine levels were reduced by nitroxides but not (*)NO. Overall, these studies demonstrate that (*)NO and nitroxides are efficient near-stoichiometric scavengers of protein radicals and, hence, are potential protective agents against protein oxidation reactions and resulting damage. These reactions show little dependence on nitroxide structure or charge.
The Heart Research Institute, 114 Pyrmont Bridge Road, Camperdown, NSW, Australia.
Magdalena A
MA
Lam
David I
DI
Pattison
Steven E
SE
Bottle
Daniel J
DJ
Keddie
Michael J
MJ
Davies
D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000737:chemistry; D009569:Nitric Oxide / Q000494:pharmacology*; D009589:Nitrogen Oxides / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011506:Proteins / Q000737:chemistry*
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D005609:Free Radicals; D009589:Nitrogen Oxides; D011506:Proteins; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; C039900:nitroxyl; C003959:TEMPO