Expression of cell death-associated phospho-c-Jun and p53-activated gene 608 in hippocampal CA1 neurons following global ischemia

Persistent activation of c-Jun N-terminal kinases (JNKs) and phosphorylatio n of c-Jun has been shown in various cell death paradigms. Inhibition of th e JNK signal transduction pathway prevented neuronal cell death both in vit ro and in vivo. In the present study, nuclear phospho-c-Jun immunoreactivit y became apparent selectively in vulnerable hippocampal CA1 neurons at 24 h after transient global cerebral ischemia. A high constitutive expression o f phospho-JNK1 was detected by immunoblot analysis of hippocampal extracts. Expression of JNK interacting protein-1 (JIP-1), which facilitates JNK sig naling, remained unchanged in post-ischemic hippocampal neurons. By contras t, p53-activated gene 608 (PAG608), which promotes cell death in vitro, was strongly induced in post-ischemic CA1 neurons. Our data suggest that trans cription factors p53 and phospho-c-Jun may contribute to programmed CA1 cel l death following ischemia. (C) 1999 Elsevier Science B.V. All rights reser ved.