NO-Redox Paradox: Direct Oxidation of alpha-Tocopherol and alpha-Tocopherol-Mediated Oxidation of Ascorbate

摘要

Nitric oxide (NO) can act as both a pro- or an antioxidant, yielding eithercytotoxic 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 a-tocopherol/ascorbate redox cycle is central to antioxidant protection, we studied the direct effects of NO on a-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. a-Tocopherol, however, in the presence of NO and under anaerobic conditions, was oxidized to the a-tocopheroxyl radical. Under conditions where NO oxidized a-tocopherol, the subsequent production of the a-tocopheroxyl radical depleted ascorbate, yielding the sernidehydroascorbyl radical and regenerating a-tocopherol. Thus, NO interacts with the redox cycle involving a-tocopherol and ascorbate in a pro-oxidant manner.