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

Ann N Y Acad Sci. 1998 Dec 11;865:111-7. doi: 10.1111/j.1749-6632.1998.tb11169.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cerebral Ventricles / drug effects
  • Cerebral Ventricles / physiology*
  • Cerebral Ventricles / physiopathology
  • Hippocampus / drug effects*
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Infusions, Intravenous
  • Infusions, Parenteral
  • Interleukin-6 / analysis
  • Ischemic Attack, Transient / physiopathology*
  • Models, Neurological
  • Neurons / drug effects*
  • Neurons / pathology
  • Neurons / physiology
  • Neuropeptides / administration & dosage
  • Neuropeptides / pharmacology*
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Rats
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • Adcyap1 protein, rat
  • Interleukin-6
  • Neuropeptides
  • Neuroprotective Agents
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Calcium-Calmodulin-Dependent Protein Kinases