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.
Lam
Magdalena A
MA
The Heart Research Institute, 114 Pyrmont Bridge Road, Camperdown, NSW, Australia.
Pattison
David I
DI
Bottle
Steven E
SE
Keddie
Daniel J
DJ
Davies
Michael J
MJ
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