Nuclear factor-κB mediates the cell survival-promoting action of activity-dependent neurotrophic factor peptide-9

Gordon W. Glazner, Simonetta Camandola, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

Activity-dependent neurotrophic factor (ADNF) is produced by astrocytes in response to neuronal depolarization and, in turn, promotes neuronal survival. A nine-amino acid ADNF peptide (ADNF9) exhibits full neurotrophic activity and potently protects cultured embryonic rat hippocampal neurons from oxidative injury and apoptosis. Picomolar concentrations of ADNF9 induced an increase in nuclear factor-κB (NF-κB) DNA-binding activity within 1 h of exposure, with a maximum increase of ~10-fold by 6 h. Activation of NF-κB was correlated with increased resistance of neurons to apoptosis induced by exposure to Fe2+. The antiapoptotic action of ADNF9 was abolished when NF-κB activation was specifically blocked with KB decoy DNA. Oxidative stress was attenuated in neurons pretreated with ADNF9, and this effect of ADNF9 was blocked by κB decoy DNA, suggesting that ADNF9 suppresses apoptosis by reducing oxidative stress. ADNF9 also prevented neuronal apoptosis following trophic factor withdrawal via an NF-κB-mediated mechanism. Thus, NF-κB mediates the neuron survival-promoting effects of ADNF9 in experimental models relevant to developmental neuronal death and neurodegenerative disorders.

Original languageEnglish (US)
Pages (from-to)101-108
Number of pages8
JournalJournal of Neurochemistry
Volume75
Issue number1
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Activity-dependent neurotrophic factor
  • Alzheimer's disease
  • Apoptosis
  • Decoy DNA
  • Hippocampus
  • Oxidative stress
  • Transcription

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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