PACAP protects hippocampal neurons against apoptosis: Involvement of JNK/SAPK signaling pathway

Seiji Shioda, Hiroshi Ozawa, Kenji Dohi, Hidekatsu Mizushima, Kiyoshi Matsumoto, Shigeo Nakajo, Atsushi Takaki, Chengji Zhou, Yasumitsu Nakai, Akira Arimura

Research output: Contribution to journalArticle

109 Scopus citations


We have demonstrated that the ischemia-induced apoptosis of neurons in the CA1 region of the rat hippocampus was prevented by either intracerebroventricular or intravenous infusion of pituitary adenylate cyclase-activating polypeptide (PACAP). However, the molecular mechanisms underlying the anti-apoptotic effect of PACAP remain to be determined. Within 3-6 h after ischemia, the activities of members of the mitogen-activated protein (MAP) kinase family, including extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK), and p38 were increased in the hippocampus. The ischemic stress had a potent influence on the MAP kinase family, especially on JNK/SAPK. PACAP inhibited the activation of JNK/SAPK after ischemic stress. Secretion of interleukin-6 (IL-6) into the cerebrospinal fluid was intensely stimulated after PACAP infusion. IL-6 inhibited the activation of JNK/SAPK, while it activated ERK. These observations suggest that PACAP and IL-6 act to inhibit the JNK/SAPK signaling pathway, thereby protecting neurons against apoptosis.

Original languageEnglish (US)
Pages (from-to)111-117
Number of pages7
JournalAnnals of the New York Academy of Sciences
StatePublished - 1998
Externally publishedYes


ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Shioda, S., Ozawa, H., Dohi, K., Mizushima, H., Matsumoto, K., Nakajo, S., Takaki, A., Zhou, C., Nakai, Y., & Arimura, A. (1998). PACAP protects hippocampal neurons against apoptosis: Involvement of JNK/SAPK signaling pathway. Annals of the New York Academy of Sciences, 865, 111-117.