L-tyrosine and nitric oxide synergize to prevent cytotoxic effects of superoxide

We found previously that the nitric oxide donor DEA/NO enhanced lipid perox idation, DNA fragmentation, and cytotoxicity in human bronchial epithelial cells (BEAS-2B) when they were cultured in LHC-8 medium containing the supe roxide-generating system hypoxanthine/xanthine oxidase (HX/XO). We have now discovered that DEA/NO's prooxidant action can be reversed by raising the L-tyrosine concentration from 30 to 400 muM. DEA/NO also protected the cell s when they were cultured in Dulbecco's Modified Eagle's Medium (DMEM), who se standard concentration Of L-tyrosine is 400 muM. Similar trends were see n with the colon adenoma cell line CaCo-2. Since HPLC analysis of cell-free DMEM or LHC-8 containing 400 PM L-tyrosine, DEA/NO, and HX/XO revealed no evidence of L-tyrosine nitration, our data suggest the existence of an as-y et uncharacterized mechanism by which L-tyrosine can influence the biochemi cal and toxicological effects of reactive nitrogen species. (C) 2001 Elsevi er Science Ireland Ltd. All rights reserved.