title: Tumor necrosis factor alpha activates NF-kappaB in acid sphingomyelinase-deficient mouse embryonic fibroblasts.
abstract: Tumor necrosis factor alpha (TNF-alpha) is one of the most potent inducer of the nuclear transcription factor kappaB (NF-kappaB). Activation of NF-kappaB is initiated by phosphorylation of the inhibitory subunit of the IkappaB-alpha-NF-kappaB complex. This leads to the dissociation of the complex and degradation of IkappaB-alpha. NF-kappaB is translocated into the nucleus. The sphingomyelin pathway is thought to mediate the TNF-alpha-induced activation of NF-kappaB by its second messenger ceramide. We have used the recently established acid sphingomyelinase-deficient mouse line (asmase-/- mice) to evaluate the role of acid sphingomyelinase in the TNF-alpha-induced signal transduction pathway. Here we present experimental evidence that acid sphingomyelinase is not involved in the TNF-alpha-induced activation of NF-kappaB. TNF-alpha treatment induced the dissociation and degradation of IkappaB-alpha and the nuclear translocation of NF-kappaB in embryonic fibroblasts derived from asmase-/- and wild type mice indiscriminately.
authors.affiliation: Neuroscience Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Cologne, Joseph-Stelzmann-Strasse 52, D-50931 Cologne, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Zumbansen
authors.forename: W
authors.initials: W
authors.lastname: Stoffel
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism; D004622:Embryo, Mammalian; D005347:Fibroblasts; D006801:Humans; D020672:I-kappa B Proteins; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D046911:Macromolecular Substances; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D013108:Sphingomyelin Phosphodiesterase