Lam, Magdalena

Pattison, David

Bottle, Steven E

Keddie, Daniel

Davies, Michael

2008

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 H₂O₂-activated horseradish peroxidase, radicals formed on myoglobin via reaction with H₂O₂, and carbon-centered radicals formed from amino acid hydroperoxides on exposure to Fe²⁺-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.

Chemical Research in Toxicology, 21(11), p. 2111-2119

1520-5010

0893-228X

https://hdl.handle.net/1959.11/13011

American Chemical Society

Nitric Oxide and Nitroxides Can Act as Efficient Scavengers of Protein-Derived Free Radicals

Journal Article

Publication