Differential alterations of NF-κB to oxidative stress in primary basal forebrain cultures

Zezong Gu, Lisa Cain, K. Werrbach-Perez, J. Regino Perez-Polo

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    17 Scopus citations

    Abstract

    Oxidative stress has been linked to neuronal cell death resulting from either acute insults due to ischemia, trauma, excitotoxicity, or chronic neurodegenerative diseases. Cholinergic basal forebrain neurons (CBFNs) compete for nerve growth factor (NGF) synthesized in the hippocampus and cortex via retrograde transport. NGF affects CBFN survival and cholinergic function via activation of the NF-κB transcription factor and this signaling pathway appears to be impaired in aged rats. Here, we demonstrate that activation of NF-κB in basal forebrain primary culture via treatment with hydrogen peroxide or TNF-alpha is predominantly restricted to CBFNs, and that NF-κB activation appears to mostly affect p65 translocation to the nucleus, but not the p50 subunit. These results are consistent with NF-κB activation being a part of recovery processes after acute oxidative stress. Since p50 or p49 (also called p52) binding to promoter sites does not stimulate transcription - both p50 and p49 lack an activating domain - and p65 does contain an activating domain and thus can act as a transcription enhancer, differential translocation of different NF-κB dimers can act as repressors of constitutive activity or enhancers. These results are in agreement with the hypothesis that p50/p65 is the active trans-activating species of NF-κB, as compared to p50/p50 homodimers which bind to NF-κB binding sites but do not trans-activate promoters. Our results also suggest that selective activation of different NF-κB dimer species may have regulatory significance in neuronal responses to acute or chronic insults to CNS. Thus, increased p65 translocation could have enhancing effects while increased p50 translocation could have a repressor role. Manipulation of the types of NF-κB species being translocated could provide a basis for therapeutic strategies. Copyright (C) 2000 ISDN.

    Original languageEnglish (US)
    Pages (from-to)185-192
    Number of pages8
    JournalInternational Journal of Developmental Neuroscience
    Volume18
    Issue number2-3
    DOIs
    StatePublished - Jun 1 2000

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    Keywords

    • Cholinergic basal forebrain neuron
    • Nerve growth factor
    • Nuclear factor-κB
    • Oxidative stress

    ASJC Scopus subject areas

    • Developmental Neuroscience
    • Developmental Biology

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