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

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Abstract

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
Volume865
DOIs
StatePublished - 1998
Externally publishedYes

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Pituitary Adenylate Cyclase-Activating Polypeptide
Heat-Shock Proteins
Protein Kinases
Neurons
Phosphotransferases
Apoptosis
Interleukin-6
Extracellular Signal-Regulated MAP Kinases
Mitogen-Activated Protein Kinases
Hippocampus
Ischemia
Intraventricular Infusions
Chemical activation
Intravenous Infusions
Cerebrospinal fluid
Cerebrospinal Fluid
p38 Mitogen-Activated Protein Kinases
Neuron
Protein
Pathway

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

PACAP protects hippocampal neurons against apoptosis : Involvement of JNK/SAPK signaling pathway. / Shioda, Seiji; Ozawa, Hiroshi; Dohi, Kenji; Mizushima, Hidekatsu; Matsumoto, Kiyoshi; Nakajo, Shigeo; Takaki, Atsushi; Zhou, Chengji; Nakai, Yasumitsu; Arimura, Akira.

In: Annals of the New York Academy of Sciences, Vol. 865, 1998, p. 111-117.

Research output: Contribution to journalArticle

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, vol. 865, pp. 111-117. https://doi.org/10.1111/j.1749-6632.1998.tb11169.x
Shioda, Seiji ; Ozawa, Hiroshi ; Dohi, Kenji ; Mizushima, Hidekatsu ; Matsumoto, Kiyoshi ; Nakajo, Shigeo ; Takaki, Atsushi ; Zhou, Chengji ; Nakai, Yasumitsu ; Arimura, Akira. / PACAP protects hippocampal neurons against apoptosis : Involvement of JNK/SAPK signaling pathway. In: Annals of the New York Academy of Sciences. 1998 ; Vol. 865. pp. 111-117.
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