Nitric oxide and nitroxides can act as efficient scavengers of protein-derived free radicals

TY - JOUR

T1 - Nitric oxide and nitroxides can act as efficient scavengers of protein-derived free radicals

AU - Lam, Magdalena A

AU - Pattison, David I

AU - Bottle, Steven E

AU - Keddie, Daniel J

AU - Davies, Michael Jonathan

PY - 2008/11

Y1 - 2008/11

N2 - 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.

AB - 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.

KW - Cyclic N-Oxides

KW - Electron Spin Resonance Spectroscopy

KW - Free Radical Scavengers

KW - Free Radicals

KW - Hydrogen Peroxide

KW - Nitric Oxide

KW - Nitrogen Oxides

KW - Oxidation-Reduction

KW - Proteins

U2 - 10.1021/tx800183t

DO - 10.1021/tx800183t

M3 - Journal article

C2 - 18834151

SN - 0893-228X

VL - 21

SP - 2111

EP - 2119

JO - Chemical Research in Toxicology

JF - Chemical Research in Toxicology

IS - 11

ER -