Sr. Bruckner et al., JNK3 contributes to c-Jun activation and apoptosis but not oxidative stress in nerve growth factor-deprived sympathetic neurons, J NEUROCHEM, 78(2), 2001, pp. 298-303
The stress activated protein kinase pathway culminates in c-Jun phosphoryla
tion mediated by the Jun Kinases (JNKs). The role of the JNK pathway in sym
pathetic 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 selecti
vely 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 inducti
on. Here, we report that oxidative stress in neurons from JNK3-deficient mi
ce is normal after NGF deprivation. In contrast, NGF-deprivation-induced in
creases in the levels of phosphorylated c-jun, c-jun, and apoptosis are eac
h inhibited in JNK3-deficient mice, Overall, these results indicate that JN
K3 plays a critical role in activation of c-Jun and apoptosis in a classic
model of cell-autonomous programmed neuron death.