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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
| Content Provider | Scilit |
|---|---|
| Author | 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 |
| Copyright Year | 2011 |
| Description | Journal: Journal of Neurochemistry International audiencePituitary 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 |
| Related Links | http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2011.07486.x/pdf |
| Ending Page | 931 |
| Page Count | 12 |
| Starting Page | 920 |
| e-ISSN | 14714159 |
| DOI | 10.1111/j.1471-4159.2011.07486.x |
| Journal | Journal of Neurochemistry |
| Issue Number | 5 |
| Volume Number | 119 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2011-12-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Neurochemistry Biochemistry and Molecular Biology Cerebellar Granule Neurons Pituitary Adenylate Cyclase‐activating Polypeptide Tissue Plasminogen Activator |
| Content Type | Text |
| Resource Type | Article |
