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PACAP‐38 Protects Cerebellar Granule Cells from Apoptosis
Author(s) -
JOURNOT LAURENT,
VILLALBA MARTIN,
BOCKAERT JOËL
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb11168.x
Subject(s) - pituitary adenylate cyclase activating peptide , cerebellum , apoptosis , kinase , mapk/erk pathway , adenylate kinase , protein kinase a , endocrinology , microbiology and biotechnology , chemistry , medicine , vasoactive intestinal peptide , dna fragmentation , glucagon , signal transduction , biology , receptor , neuropeptide , programmed cell death , biochemistry , hormone
A bstract : 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.