Tumor necrosis factor-alpha and nerve growth factor synergistically induce iNOS in pheochromocytoma cells.
Inducible nitric oxide synthase (iNOS) has been reported in tangle-bearing neurons of patients with Alzheimer's disease (AD), and can be induced by tumor necrosis factor-alpha (TNFalpha). High CNS levels of TNFalpha are associated with neurodegenerative diseases such as AD, where neurons dependent on neurotrophins such as nerve growth factor (NGF) are particularly affected. In this study we determined the effect of TNFalpha on iNOS in NGF-responsive pheochromocytoma (PC12) cells. We found that while TNFalpha and NGF alone were unable to induce iNOS, their simultaneous addition resulted in iNOS induction and the release of nitric oxide. Our results suggest that synergistic iNOS induction by TNFalpha and NGF may occur in selective population of NGF-responsive neurons in the presence of elevated CNS levels of TNFalpha.
Macdonald
N J
NJ
Department of Anatomy and Neuroscience, Marine Biomedical Institute, University of Texas Medical Branch, Galveston 77555, USA.
Taglialatela
G
G
D000310:Adrenal Gland Neoplasms / Q000201:enzymology; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D026121:Indole Alkaloids; D020932:Nerve Growth Factor / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D016716:PC12 Cells; D010673:Pheochromocytoma / Q000201:enzymology; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D014409:Tumor Necrosis Factor-alpha; D020932:Nerve Growth Factor; C049985:staurosporine aglycone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat