Oxidative stress activates transcription factor Nf-κB-mediated protective signaling in primary rat neuronal cultures

Ella Kratsovnik, Yael Bromberg, Oded Sperling, Esther Zoref-Shani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Activation of transcription factor nuclear factor-κB (NF-κB) can result in enhanced de novo synthesis of both proteins that confer protection and those that cause death. The present study was undertaken to clarify in primary neuronal cultures the consequences of the oxidative stress-induced activation of NF-κB and mediation of death or survival signals. The neuronal cultures were exposed to chemical ischemia (iodoacetic acid), followed by reperfusion (I/R insult). This insult injured the neurons, as manifested in a 7- to 10-fold increase in LDH release, and decreased the cellular content of IκBα by 55-65 %, indicating NF-κB activation. The antioxidants LY231617, melatonin, and sodium salicylate and the antioxidant and inhibitor of NF-κB activation pyrrolidine dithiocarbamate, protected the neurons against the insult and prevented the decrease in cellular IκBα content. In contrast, inhibition of NF-κB translocation by SN50 inbothuninsulted and insulted neuronal cultures resulted in a 2.9- and 2.4-fold increase in LDH release, respectively. The results indicate that the insult-induced oxidative stress activates transcription factor NF-κB associated with induction of protection and suggest that constitutive activation of NF-κB under physiological conditions acts to protect the neurons against physiological injury.

Original languageEnglish
Pages (from-to)27-32
Number of pages6
JournalJournal of Molecular Neuroscience
Volume26
Issue number1
DOIs
StatePublished - May 2005

Funding

FundersFunder number
Hirsh and Gania Wasserman Fund
Sackler Faculty of Medicine

    Keywords

    • Antioxidants
    • IκBα
    • Pyrrolidine dithiocarbamate (PDTC)
    • Reactive oxygen species (ROS)
    • SN50
    • Transcription factor nuclear factor-κB (NF-κB)

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