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Involvement of stathmin 1 in the neurotrophic effects of PACAP in PC12 cells
Author(s) -
Dejda Agnieszka,
Chan Philippe,
Seaborn Tommy,
Coquet Laurent,
Jouenne Thierry,
Fournier Alain,
Vaudry Hubert,
Vaudry David
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06873.x
Subject(s) - stathmin , neurotrophin , phosphorylation , protein kinase a , adenylate kinase , pituitary adenylate cyclase activating peptide , biology , neurite , microbiology and biotechnology , neurotrophic factors , kinase , western blot , neuroprotection , chemistry , vasoactive intestinal peptide , biochemistry , neuropeptide , receptor , neuroscience , gene , in vitro
J. Neurochem. (2010) 114 , 1498–1510. Abstract Rat pheochromocytoma PC12 cells have been widely used to investigate the neurotrophic activities of pituitary adenylate cyclase‐activating polypeptide (PACAP). In particular, PACAP has been shown to promote differentiation and to inhibit apoptosis of PC12 cells. In order to identify the mechanisms mediating these effects, we sought for proteins that are phosphorylated upon PACAP treatment. High‐performance liquid chromatography and 2D gel electrophoresis analysis, coupled with mass spectrometry, revealed that stathmin 1 is strongly phosphorylated within only 5 min of exposure to PACAP. Western blot experiments confirmed that PACAP induced a robust phosphorylation of stathmin 1 in a time‐dependent manner. On the other hand, PACAP decreased stathmin 1 gene expression. Investigations of the signaling mechanisms known to be activated by PACAP revealed that phosphorylation of stathmin 1 was mainly mediated through the protein kinase A and mitogen‐activated protein kinase pathways. Blockage of stathmin 1 expression with small interfering RNA did not affect PC12 cell differentiation induced by PACAP but reduced the ability of the peptide to inhibit caspase 3 activity and significantly decreased its neuroprotective action. Taken together, these data demonstrate that stathmin 1 is involved in the neurotrophic effect of PACAP in PC12 cells.