TY - JOUR
T1 - 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
AU - Pannaccione, Anna
AU - Secondo, Agnese
AU - Scorziello, Antonella
AU - Calì, Gaetano
AU - Taglialatela, Maurizio
AU - Annunziato, Lucio
PY - 2005/8
Y1 - 2005/8
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Intracellular Ca concentration
KW - Neuronal cell death
KW - Nuclear factor-κB
KW - Reactive oxygen species
KW - Voltage-gated K channels
UR - http://www.scopus.com/inward/record.url?scp=23244453593&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23244453593&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2005.03075.x
DO - 10.1111/j.1471-4159.2005.03075.x
M3 - Article
C2 - 15969743
AN - SCOPUS:23244453593
VL - 94
SP - 572
EP - 586
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 3
ER -