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Pituitary adenylate cyclase‐activating polypeptide (PACAP) stimulates the expression and the release of tissue plasminogen activator (tPA) in neuronal cells: involvement of tPA in the neuroprotective effect of PACAP
Author(s) -
Raoult Emilie,
Roussel Benoît Denis,
Bénard Magalie,
Lefebvre Thomas,
Ravni Aurélia,
Ali Carine,
Vivien Denis,
Komuro Hitoshi,
Fournier Alain,
Vaudry Hubert,
Vaudry David,
Galas Ludovic
Publication year - 2011
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.1471-4159.2011.07486.x
Subject(s) - tissue plasminogen activator , adenylate kinase , plasminogen activator , activator (genetics) , pituitary adenylate cyclase activating peptide , cyclase , protein kinase a , chemistry , t plasminogen activator , plasminogen activator inhibitor 1 , neurotrophin , biology , endocrinology , medicine , kinase , microbiology and biotechnology , biochemistry , neuropeptide , vasoactive intestinal peptide , receptor
J. Neurochem. (2011) 119 , 920–931. Abstract Pituitary adenylate cyclase‐activating polypeptide (PACAP) and tissue plasminogen activator (tPA) play important roles in neuronal migration and survival. However, a direct link between the neurotrophic effects of PACAP and tPA has never been investigated. In this study, we show that, in PC12 cells, PACAP induced a 9.85‐fold increase in tPA gene expression through activation of the protein kinase A‐ and protein kinase C‐dependent signaling pathways. In immature cerebellar granule neurons (CGN), PACAP stimulated tPA mRNA expression and release of proteolytically active tPA. Immunocytochemical labeling revealed the presence of tPA in the cytoplasm and processes of cultured CGN. The inhibitory effect of PACAP on CGN motility was not affected by the tPA substrate plasminogen or the tPA inhibitor plasminogen activator inhibitor‐1. In contrast, plasminogen activator inhibitor‐1 significantly reduced the stimulatory effect of PACAP on CGN survival. Altogether, these data indicate that tPA gene expression is activated by PACAP in both tumoral and normal neuronal cells. The present study also demonstrates that PACAP stimulates the release of tPA which promotes CGN survival by a mechanism dependent of its proteolytic activity.