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

  1. Author:
    Souici, A. C.
    Fitzhugh, A. L.
    Keefer, L. K.
    Felley-Bosco, E.

  2. Author Address

    Inst Pharmacol & Toxicol, Bugnon 27, CH-1005 Lausanne, Switzerland. Inst Pharmacol & Toxicol, CH-1005 Lausanne, Switzerland. NCI, Intramural Res Support Program, SAIC, Frederick, MD 21702 USA. NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Felley-Bosco E Inst Pharmacol & Toxicol, Bugnon 27, CH-1005 Lausanne, Switzerland.
    1. Year: 2001
  2. Journal: Toxicology
    1. 165
    2. 2-3
    3. Pages: 163-170
  4. Type of Article: Article
  1. Abstract:

    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 muM. 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 muM. Similar trends were seen 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-yet uncharacterized mechanism by which L-tyrosine can influence the biochemical and toxicological effects of reactive nitrogen species. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

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