NGF-resistant PC12 cell death induced by arachidonic acid is accompanied by a decrease of active PKC zeta and nuclear factor kappa B

Nancy J. Macdonald, J. Regino Perez-Polo, Adrianne D. Bennett, Giulio Taglialatela

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Inflammation and the associated release of inflammatory cytokines such as tumor necrosis factor alpha (TNFα) may he a component of neurodegenerative diseases associated with aging or chronic HIV-1 infection. Most of the neurons that are affected under these conditions require a constant supply of trophic factors such as nerve growth factor (NGF) for survival. NGF acts via binding to a specific tyrosine kinase receptor (TrkA). NGF also binds to the common neurotrophin receptor (p75(NTR)), a member of the TNFα receptor (TNFR-I) superfamily, whose function may be to modulate apoptosis via the release of ceramide and the activation of the transcription factor nuclear factor kappa B (NFκB). The similarity between p75(NTR) and TNFR-I signal transduction pathways suggests that one of the mechanisms by which TNFα affects neuronal survival is by impacting upon these pathways that normally promote NGF support of neurons. Here we show that arachidonic acid (AA), a signaling lipid potentially associated with TNFR-I signal cascade, induces apoptosis in PC12 cells through inhibition of both protein kinase C zeta (PKCζ) and NFκB activity. We also show that apoptosis induced by AA cannot be prevented by NGF. These data support the idea that PKCζ and NFκB are both essential signaling elements for mediating NGF-promoted rescue from apoptosis. Our results also suggest that AA, an inflammatory signal lipid induced by TNFα via binding to TNFR-I, may reduce neuronal survival by inhibiting elements of the signal cascade induced by NGF.

Original languageEnglish (US)
Pages (from-to)219-226
Number of pages8
JournalJournal of Neuroscience Research
Volume57
Issue number2
DOIs
StatePublished - Jul 15 1999

Keywords

  • Apoptosis
  • Arachidonic acid
  • Inflammation
  • NFκB
  • Nerve growth factor (NGF)
  • PKCζ
  • TNFα

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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