Abstract
Pituitary adenylate cyclase-activating polypeptides (PACAP-27 and -38) are neuropeptides of the vasoactive intestinal polypeptide (VIP)/secretin/glucagon family. PACAP receptors are expressed in different brain regions including the cerebellum. We used primary culture of rat cerebellar granule neurons to study the effect of PACAP-38 on apoptosis induced by potassium deprivation. We demonstrated that serum and potassium withdrawal induces a mixture of apoptosis and necrosis rather than apoptosis only. We showed that PACAP-38 increased survival of cerebellar neurons in a dose-dependent manner by specifically decreasing the extent of apoptosis estimated by DNA fragmentation. PACAP-38 induced activation of the extracellular signal-regulated kinase (ERK)-type of MAP kinase through a cAMP-dependent pathway. PD98059, an inhibitor of MEK (MAP kinase kinase), completely abolished the anti-apoptotic effect of PACAP-38, suggesting that MAP kinase pathway activation is necessary for PACAP-38 effect.
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / physiology*
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cells, Cultured
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Cerebellum / cytology*
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Cerebellum / physiology*
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DNA Fragmentation
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Enzyme Inhibitors / pharmacology
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Flavonoids / pharmacology
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Mitogen-Activated Protein Kinase Kinases
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Necrosis
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Neurons / cytology
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Neurons / drug effects*
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Neurons / physiology
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Neuropeptides / pharmacology*
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Neuropeptides / physiology
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Neuroprotective Agents / pharmacology*
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Pituitary Adenylate Cyclase-Activating Polypeptide
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Potassium / pharmacology
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Protein Kinases / metabolism
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Rats
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Pituitary Hormone / genetics
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Receptors, Pituitary Hormone / physiology
Substances
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Adcyap1 protein, rat
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Enzyme Inhibitors
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Flavonoids
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Neuropeptides
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Neuroprotective Agents
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Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Pituitary Hormone
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Protein Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase Kinases
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Potassium
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one