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Genetic and redox determinants of nitric oxide cytotoxicity in a Salmonella typhimurium model.
Title | Genetic and redox determinants of nitric oxide cytotoxicity in a Salmonella typhimurium model. |
Publication Type | Journal Article |
Year of Publication | 1995 |
Authors | De Groote, MA, Granger, D, Xu, Y, Campbell, G, Prince, R, Fang, FC |
Journal | Proc Natl Acad Sci U S A |
Volume | 92 |
Issue | 14 |
Pagination | 6399-403 |
Date Published | 1995 Jul 3 |
ISSN | 0027-8424 |
Keywords | Base Sequence, DNA Primers, Genes, Bacterial, Glutathione, Microbial Sensitivity Tests, Molecular Sequence Data, Molsidomine, Mutagenesis, Nitrates, Nitric Oxide, Nitroso Compounds, Oxidation-Reduction, Polyamines, S-Nitrosoglutathione, Salmonella typhimurium, Species Specificity, Vasodilator Agents |
Abstract | Paradoxically, nitric oxide (NO) has been found to exhibit cytotoxic, antiproliferative, or cytoprotective activity under different conditions. We have utilized Salmonella mutants deficient in antioxidant defenses or peptide transport to gain insights into NO actions. Comparison of three NO donor compounds reveals distinct and independent cellular responses associated with specific redox forms of NO. The peroxynitrite (OONO-) generator 3-morpholinosydnonimine hydrochloride mediates oxygen-dependent Salmonella killing, whereas S-nitrosoglutathione (GSNO) causes oxygen-independent cytostasis, and the NO. donor diethylenetriamine-nitric oxide adduct has no antibacterial activity. GSNO has the greatest activity for stationary cells, a characteristic relevant to latent or intracellular pathogens. Moreover, the cytostatic activity of GSNO may best correlate with antiproliferative or antimicrobial effects of NO, which are unassociated with overt cell injury. dpp mutants defective in active dipeptide transport are resistant to GSNO, implicating heterolytic NO+ transfer rather than homolytic NO. release in the mechanism of cytostasis. This transport system may provide a specific pathway for GSNO-mediated signaling in biological systems. The redox state and associated carrier molecules are critical determinants of NO activity. |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
PubMed ID | 7604003 |
PubMed Central ID | PMC41525 |
Grant List | AI32463 / AI / NIAID NIH HHS / United States |