Coinduction of nitric oxide synthesis and intracellular nonheme iron-nitrosyl complexes in murine cytokine-treated fibroblasts.
Murine fibroblasts treated with interferon-gamma plus tumor necrosis factor-alpha plus lipopolysaccharide produce nitrite and EPR-observable intracellular nonheme iron-thiol-dinitrosyl species. Inhibition of .NO synthesis or de novo tetrahydrobiopterin (BH4) synthesis decreases nitrite and the EPR signal. The effects of BH4 synthesis inhibition are prevented by sepapterin, which increases BH4 through the salvage pathway.
Lancaster
J R
JR
Department of Surgery, University of Pittsburgh, School of Medicine, PA 15261.
Werner-Felmayer
G
G
Wachter
H
H
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001708:Biopterins / Q000031:analogs & derivatives / Q000096:biosynthesis; D016207:Cytokines / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D004926:Escherichia coli; D005290:Ferric Compounds / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D007042:Hypoxanthines / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019323:omega-N-Methylarginine
D016207:Cytokines; D005290:Ferric Compounds; D007042:Hypoxanthines; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D001708:Biopterins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D001120:Arginine; D007501:Iron; C017202:2,4-diaminohypoxanthine; C003402:sapropterin