JNK3 contributes to c-Jun activation and apoptosis but not oxidative stress in nerve growth factor-deprived sympathetic neurons

Shane R. Bruckner, Steven P. Tammariello, Chia Yi Kuan, Richard A. Flavell, Pasko Rakic, Steven Estus

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

The stress activated protein kinase pathway culminates in c-Jun phosphorylation mediated by the Jun Kinases (JNKs). The role of the JNK pathway in sympathetic neuronal death is unclear in that apoptosis is not inhibited by a dominant negative protein of one JNK kinase, SEK1, but is inhibited by CEP-1347, a compound known to inhibit this overall pathway but not JNKs per se. To evaluate directly the apoptotic role of the JNK isoform that is selectively expressed in neurons, JNK3, we isolated sympathetic neurons from JNK3-deficient mice and quantified nerve growth factor (NGF) deprivation-induced neuronal death, oxidative stress, c-Jun phosphorylation, and c-jun induction. Here, we report that oxidative stress in neurons from JNK3-deficient mice is normal after NGF deprivation. In contrast, NGF-deprivation-induced increases in the levels of phosphorylated c-Jun, c-jun, and apoptosis are each inhibited in JNK3-deficient mice. Overall, these results indicate that JNK3 plays a critical role in activation of c-Jun and apoptosis in a classic model of cell-autonomous programmed neuron death.

Original languageEnglish
Pages (from-to)298-303
Number of pages6
JournalJournal of Neurochemistry
Volume78
Issue number2
DOIs
StatePublished - 2001

Keywords

  • Apoptosis
  • JNK
  • NGF
  • Oxidative stress
  • Programmed cell death
  • Sympathetic neuron

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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