L-tyrosine and nitric oxide synergize to prevent cytotoxic effects of superoxide.
We found previously that the nitric oxide donor DEA/NO enhanced lipid peroxidation, DNA fragmentation, and cytotoxicity in human bronchial epithelial cells (BEAS-2B) when they were cultured in LHC-8 medium containing the superoxide-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 microM. DEA/NO also protected the cells when they were cultured in Dulbecco's Modified Eagle's Medium (DMEM), whose standard concentration of L-tyrosine is 400 microM. Similar trends were seen with the colon adenoma cell line CaCo-2. Since HPLC analysis of cell-free DMEM or LHC-8 containing 400 microM L-tyrosine, DEA/NO, and HX/XO revealed no evidence of L-tyrosine nitration, our data suggest the existence of an as-yet uncharacterized mechanism by which L-tyrosine can influence the biochemical and toxicological effects of reactive nitrogen species.
Souici
A C
AC
Institute of Pharmacology and Toxicology, Bugnon 27, 1005, Lausanne, Switzerland.
Fitzhugh
A L
AL
Keefer
L K
LK
Felley-Bosco
E
E
D001980:Bronchi / Q000166:cytology / Q000187:drug effects; D018938:Caco-2 Cells / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004357:Drug Synergism; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology* / Q000633:toxicity; D019271:Hypoxanthine / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology* / Q000633:toxicity; D020030:Nitric Oxide Donors / Q000494:pharmacology* / Q000633:toxicity; D009589:Nitrogen Oxides; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity*; D014443:Tyrosine / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000378:metabolism
D006834:Hydrazines; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D017382:Reactive Oxygen Species; D013481:Superoxides; D019271:Hypoxanthine; D009569:Nitric Oxide; D014443:Tyrosine; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D014969:Xanthine Oxidase