Purinergic signaling and cell proliferation and differentiation in a neuronal pheocromocytoma PC12 cell model
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1
University of Pisa, Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, Italy
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2
University of Milan, Department of Pharmacological Sciences, Italy
Several studies point out the nucleotides play a trophic role in regenerative conditions, acting as signalling molecules in neuronal development and differentiation. Neuronal regeneration involving the formation of new neurites repairs brain injury and requires the appropriate spatial/temporal recruitment of several signalling and promoter molecules. Neurothrophins, such as nerve growth factor (NGF), are key regulators of neuronal differentiation, promoting neurite and synapse formation and maintaining neuronal survival by apoptosis resistence. Recent evidences have shown that receptor cross-talk is also an important mechanism for regulation of neurothrophin signalling in orchestrating neuronal survival/differentiation. It has been demonstrated that extracellular adenine and uridine nucleotides, through the interaction with specific purinergic receptors (i.e. P2Y2), may influence neuronal differentiation and survival regulating growth factor-mediated signalling.
We have recently reported that GPR17, a new P2Y like receptor activated by both uracyl nucleotides and leukotrienes, play an important role in neuronal differentiation and in brain local remodelling/repair response. In order to elucidate the role of GPR17 in neuronal survival/differentiation we evaluated the functional interaction between GPR17 ligands and NGF in PC12 cell model.
Experimental data showed that GPR17 is expressed in PC12 cells after 10 days NGF-mediated differentiation. In these conditions GPR17 ligands, UDP-glucose and LTD4 significantly increased cell proliferation potentiating NGF effects. Our results suggest GPR17 ligands can behave as neurothropic factor for neuronal cells, underlying a potential interplay between the receptor and NGF in the control of brain repair. Therefore, GPR17 could be a possible target for pharmacological intervention in neurodegenerative process.
Keywords:
GPR17,
intracellular pathways,
neuronal differentiation,
neurothrophins,
PC12 Cells
Conference:
3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009.
Presentation Type:
Oral Presentation
Topic:
Symposium 27 – The purinergic system as a target for the development of novel drugs for acute and chronic CNS disorders
Citation:
Trincavelli
ML,
Ciampi
O,
Lecca
D,
Daniele
S,
Abbracchio
MP and
Martini
C
(2009). Purinergic signaling and cell proliferation and differentiation in a neuronal pheocromocytoma PC12 cell model.
Front. Neurosci.
Conference Abstract:
3rd Mediterranean Conference of Neuroscience .
doi: 10.3389/conf.neuro.01.2009.16.097
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Received:
23 Nov 2009;
Published Online:
23 Nov 2009.
*
Correspondence:
Claudia Martini, University of Pisa, Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, Pisa, Italy, cmartini@farm.unipi.it