TY - JOUR
T1 - PACAP protects hippocampal neurons against apoptosis
T2 - Involvement of JNK/SAPK signaling pathway
AU - Shioda, Seiji
AU - Ozawa, Hiroshi
AU - Dohi, Kenji
AU - Mizushima, Hidekatsu
AU - Matsumoto, Kiyoshi
AU - Nakajo, Shigeo
AU - Takaki, Atsushi
AU - Zhou, Cheng Ji
AU - Nakai, Yasumitsu
AU - Arimura, Akira
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1749-6632.1998.tb11169.x
DO - 10.1111/j.1749-6632.1998.tb11169.x
M3 - Article
C2 - 9928003
AN - SCOPUS:2142725149
SN - 0077-8923
VL - 865
SP - 111
EP - 117
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
ER -