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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
- Source :
- Journal of Neurochemistry. 119:920-931
- Publication Year :
- 2011
- Publisher :
- Wiley, 2011.
-
Abstract
- 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.
- Subjects :
- endocrine system
0303 health sciences
integumentary system
biology
Chemistry
Motility
Adenylate kinase
Biochemistry
Tissue plasminogen activator
Molecular biology
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Gene expression
medicine
biology.protein
Signal transduction
Protein kinase A
Plasminogen activator
hormones, hormone substitutes, and hormone antagonists
030217 neurology & neurosurgery
030304 developmental biology
medicine.drug
Neurotrophin
Subjects
Details
- ISSN :
- 00223042
- Volume :
- 119
- Database :
- OpenAIRE
- Journal :
- Journal of Neurochemistry
- Accession number :
- edsair.doi...........d42037f3bd685a764960e005812b3738