Nuclear factor-κB activation by reactive oxygen species mediates voltage-gated K+ current enhancement by neurotoxic β-amyloid peptides in nerve growth factor-differentiated PC-12 cells and hippocampal neurones

Anna Pannaccione, Agnese Secondo, Antonella Scorziello, Gaetano Calì, Maurizio Taglialatela, Lucio Annunziato

Research output: Contribution to journalArticle

Abstract

Increased activity of plasma membrane K+ channels, leading to decreased cytoplasmic K+ concentrations, occurs during neuronal cell death. In the present study, we showed that the neurotoxic β-amyloid peptide Aβ25-35 caused a dose-dependent (0.1-10 μM) and time-dependent (> 12 h) enhancement of both inactivating and non-inactivating components of voltage-dependent K+ (VGK) currents in nerve growth factor-differentiated rat phaeochromocytoma (PC-12) cells and primary rat hippocampal neurones. Similar effects were exerted by Aβ1-42, but not by the non-neurotoxic Aβ35-25 peptide. Aβ25-35 and Aβ1-42 caused an early (15-20 min) increase in intracellular Ca2+ concentration. This led to an increased production of reactive oxygen species (ROS), which peaked at 3 h and lasted for 24 h; ROS production seemed to trigger the VGK current increase as vitamin E (50 μM) blocked both the Aβ25-35- and Aβ1-42-induced ROS increase and VGK current enhancement. Inhibition of protein synthesis (cycloheximide, 1 μg/mL) and transcription (actinomycin D, 50 ng/mL) blocked Aβ25-35-induced VGK current enhancement, suggesting that this potentiation is mediated by transcriptional activation induced by ROS. Interestingly, the specific nuclear factor-κB inhibitor SN-50 (5 μM), but not its inactive analogue SN-50M (5 μM), fully counteracted Aβ1-42- or Aβ25-35-induced enhancement of VGK currents, providing evidence for a role of this family of transcription factors in regulating neuronal K+ channel function during exposure to Aβ.

Original languageEnglish
Pages (from-to)572-586
Number of pages15
JournalJournal of Neurochemistry
Volume94
Issue number3
DOIs
Publication statusPublished - Aug 2005

Keywords

  • Alzheimer's disease
  • Intracellular Ca concentration
  • Neuronal cell death
  • Nuclear factor-κB
  • Reactive oxygen species
  • Voltage-gated K channels

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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