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 e ither cytotoxic or protective effects, respectively. The previously un recognized redox interactions of NO with antioxidants, and not solely its well-known reactions with oxygen radicals, peroxyl radicals and tr ansition metal centers, may be essential for its dual mechanisms in ce lls. Since the alpha-tocopherol/ascorbate redox cycle is central to an tioxidant protection, we studied the direct effects of NO on alpha-toc opherol, ascorbate and combinations thereof in aqueous, micellar envir onments 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 con ditions where NO oxidized alpha-tocopherol, the subsequent production of the alpha-tocopheroxyl radical depleted ascorbate, yielding the sem idehydroascorbyl radical and regenerating alpha-tocopherol. Thus, NO i nteracts with the redox cycle involving alpha-tocopherol and ascorbate in a pro-oxidant manner. (C) 1996 Academic Press, Inc.