Oxidative modulation of nuclear factor-κB in human cells expressing mutant fALS-typical superoxide dismutases

Arianna Casciati, Alberto Ferri, Mauro Cozzolino, Fulvio Celsi, Monica Nencini, Giuseppe Rotilio, Maria Teresa Carrì

Research output: Contribution to journalArticlepeer-review


Previous evidence supports the notion of a redox regulation of protein phosphatase calcineurin that might be relevant for neurodegenerative processes where an imbalance between generation and removal of reactive oxygen species occurs. We have recently observed that calcineurin activity is depressed in human neuroblastoma cells expressing Cu,Zn superoxide dismutase (SOD1) mutant G93A and in brain areas from G93A transgenic mice, and that mutant G93A-SOD1 oxidatively inactivates calcineurin in vitro. We have studied the possibility that, by interfering directly with calcineurin activity, mutant SOD1 can modulate pathways of signal transduction mediated by redox-sensitive transcription factors. In this paper, we report a calcineurin-dependent activation of nuclear factor-κB (NF-κB) induced by the expression of familial amyotrophic lateral sclerosis (fALS)-SOD1s in human neuroblastoma cell lines. Alteration of the phosphorylation state of IκBα (the inhibitor of NF-κB translocation into the nucleus) and induction of cyclooxygenase 2 are consistent with the up-regulation of this transcription factor in this system. All of these modifications might be relevant to signaling pathways involved in the pathogenesis of fALS.

Original languageEnglish
Pages (from-to)1019-1029
Number of pages11
JournalJournal of Neurochemistry
Issue number5
Publication statusPublished - Dec 2002


  • Calcineurin
  • Familial amyotrophic lateral sclerosis
  • IκBα
  • Nuclear factor-κB
  • Superoxide dismutase
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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