1. Protective role of nuclear factor kappa B against nitric oxide-induced apoptosis in J774 macrophages.
- Author
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D'Acquisto F, de Cristofaro F, Maiuri MC, Tajana G, and Carnuccio R
- Subjects
- Amino Acid Chloromethyl Ketones pharmacology, Animals, Cell Line metabolism, Cell Survival drug effects, DNA Fragmentation drug effects, DNA Fragmentation physiology, DNA-Binding Proteins drug effects, Mice, NF-KappaB Inhibitor alpha, Nitroprusside pharmacology, Apoptosis physiology, Cell Survival physiology, DNA-Binding Proteins antagonists & inhibitors, I-kappa B Proteins, Macrophages physiology, NF-kappa B physiology, Nitric Oxide metabolism
- Abstract
We investigated the role of constitutive transcription factor nuclear factor kappaB (NF-kappaB) in nitric oxide (NO)-mediated apoptosis in J774 macrophages. Our results show that NF-kappaB is present in untreated J774 cells in a form constitutively active. Incubation of cells with sodium nitroprusside (SNP) and S-nitroso-glutathione (GSNO), two NO-generating compounds, caused: (a) inhibition of constitutive NF-kappaB/DNA binding activity; (b) decrease of cell viability; (c) DNA fragmentation; (d) ApopTag positivity. Pyrrolidine dithiocarbamate (PDTC) and N-alpha-para-tosyl-L-lysine chloromethyl ketone (TLCK), two inhibitors of NF-kappaB activation, showed the same effects of both NO-generating compounds. Furthermore, SNP and GSNO as well as PDTC and TLCK significantly increased the cytoplasmic level of IkappaBalpha. All together these results demonstrate that constitutive NF-kappaB protects J774 macrophages from NO-induced apoptosis. Moreover, these findings show, for the first time, that NO-generating compounds may induce apoptosis in J774 macrophages by down-regulating constitutive NF-kappaB/DNA binding activity and suggest a novel mechanism by which NO induces apoptosis.
- Published
- 2001
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