Protective role of nuclear factor kappa B against nitric oxide-induced apoptosis in J774 macrophages

Cell Death and Differentiation
F D'AcquistoR Carnuccio

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.

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Citations

Sep 10, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Chiara LaezzaMaurizio Bifulco
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Nov 15, 2005·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Daniela De StefanoRosa Carnuccio
May 5, 2007·European Journal of Pharmacology·Daniela De StefanoRosa Carnuccio
Jun 25, 2004·The American Journal of Pathology·Maria Chiara MaiuriRosa Carnuccio
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Jun 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jay R RadkeJames L Cook

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis