NO-redox paradox: direct oxidation of alpha-tocopherol and alpha-tocopherol-mediated oxidation of ascorbate.
Nitric-oxide (NO) can act as both a pro- or an antioxidant, yielding either cytotoxic or protective effects, respectively. The previously unrecognized redox interactions of NO with antioxidants, and not solely its well-known reactions with oxygen radicals, peroxyl radicals and transition metal centers, may be essential for its dual mechanisms in cells. Since the alpha-tocopherol/ascorbate redox cycle is central to antioxidant protection, we studied the direct effects of NO on alpha-tocopherol, ascorbate and combinations thereof in aqueous, micellar environments using ESR spectral and HPLC quantitative techniques. We found that NO does not directly oxidize ascorbate under anaerobic conditions. alpha-Tocopherol, however, in the presence of NO and under anaerobic conditions, was oxidized to the alpha-tocopheroxyl radical. Under conditions where NO oxidized alpha-tocopherol, the subsequent production of the alpha-tocopheroxyl radical depleted ascorbate, yielding the semidehydroascorbyl radical and regenerating alpha-tocopherol. Thus, NO interacts with the redox cycle involving alpha-tocopherol and ascorbate in a pro-oxidant manner.
Gorbunov
N V
NV
Department of Environmental & Occupational Health, University of Pittsburgh, Pennsylvania 15238, USA.
Osipov
A N
AN
Sweetland
M A
MA
Day
B W
BW
Elsayed
N M
NM
Kagan
V E
VE
D000975:Antioxidants / Q000737:chemistry*; D001205:Ascorbic Acid / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004578:Electron Spin Resonance Spectroscopy; D007700:Kinetics; D009569:Nitric Oxide / Q000737:chemistry*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000737:chemistry*; D013997:Time Factors; D014466:Ultraviolet Rays; D014810:Vitamin E / Q000737:chemistry*
D000975:Antioxidants; D017382:Reactive Oxygen Species; D014810:Vitamin E; D009569:Nitric Oxide; D001205:Ascorbic Acid