Type

Journal Article

Authors

Jochen H M Prehn
Hans-Georg König
Heiko Düssmann
Robert Schwamborn

Subjects

Biochemistry

Topics
pharmacology hek293 cells animals animals newborn rats pc12 cells nf kappa b excitatory amino acid agonists rats sprague dawley cerebral cortex p65 oncofetal mrna transport protein rat cells cultured ultrastructure metabolism protein transport humans neoplasm proteins hippocampus cytology drug effects signal transduction cytosol genetics neurons n methylaspartate nucleocytoplasmic transport proteins calcium cell nucleolus rna small interfering cell death

Time-lapse imaging of p65 and IκBα translocation kinetics following Ca(2+)-induced neuronal injury reveals biphasic translocation kinetics in surviving neurons. (2016)

Abstract The transcription factor nuclear factor-κB (NF-κB) regulates neuronal differentiation, plasticity and survival. It is well established that excitatory neurotransmitters such as glutamate control NF-κB activity. Glutamate receptor overactivation is also involved in ischemic- and seizure-induced neuronal injury and neurodegeneration. However, little is known at the single cell-level how NF-κB signaling relates to neuronal survival during excitotoxic injury. We found that silencing of p65/NF-κB delayed N-methyl-d-aspartate (NMDA)-induced excitotoxic injury in hippocampal neurons, suggesting a functional role of p65 in excitotoxicity. Time-lapse imaging of p65 and its inhibitor IκBα using GFP and Cerulean fusion proteins revealed specific patterns of excitotoxic NF-κB activation. Nuclear translocation of p65 began on average 8±3min following 15min of NMDA treatment and was observed in up to two thirds of hippocampal neurons. Nuclear translocation of IκBα preceded that of p65 suggesting independent translocation processes. In surviving neurons, the onset of p65 nuclear export correlated with mitochondrial membrane potential recovery. Dying neurons exhibited persistent nuclear accumulation of p65-eGFP until plasma membrane permeabilization. Our data demonstrate an important role for p65 activation kinetics in neuronal cell death decisions following excitotoxic injury.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Jochen H M Prehn, Hans-Georg König, Heiko Düssmann, Robert Schwamborn

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
Hans Georg König
Royal College of Surgeons in Ireland
Total Publications: 22
 
3
Heiko Düssmann
Royal College of Surgeons in Ireland
Total Publications: 45
 
4
Robert F Schwamborn
Royal College of Surgeons in Ireland
Total Publications: 6