Τόμος 22 (2008) – Τεύχος 2 – Άρθρο 50 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Διεθνής Έκδοση – Volume 22 (2008) – Issue 2 – Article 50 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-International Edition

Title Sustained activation of CREB is required for neuronal differentiation of α2-AR transfected PC12 cells
Authors G. Karkoulias1, K. Kypreos1, P. Papathanasopoulos2 and Ch. Flordellis1

1.  Department of Pharmacology, 2. Department of Neurology, Medical School, University of Patras, Rio, Patra, Greece

Citation Karkoulias, G., Kypreos, K., Papathanasopoulos, P., Florderllis, C.: Sustained activation of CREB is required for neuronal differentiation of α2-AR transfected PC12 cells, Epitheorese Klin. Farmakol. Farmakokinet. 22(2): 185-188 (2008)
Publication Date 23-25 May 2008
Full Text Language English
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Keywords α2-Adrenergic receptor, PC12 cells, CREB, neuronal differentiation
Other Terms Review article
Summary On incubation with epinephrine, PC12 cells stably expressing α2-adrenergic receptor (α2-AR) undergo morphological and biochemical changes characteristic of neuron-like differentiation. The present study shows that α2C-AR stimulation induces sustained phosphorylation of the transcription factor CREB and sustained activity of a CRE-reporter plasmid in differentiating PC12α2C cells. Furthermore, inhibition of CREB activity with dominant negative mutant of CREB abolished the effects of epinephrine on the expression of the neuronal marker peripherin as well as neurite outgrowth. Altogether these results suggest that sustained activation of CREB is required for α2-AR-induced neuronal differentiation of PC12 cells.
References 1. Philipp M., Brede M., Hein L.: Physiological significance of α2-adrenergic receptor subtype diversity: one receptor is not enough. Am. J. Physiol. Regul. Integr. Comp. Physiol. 283: R287-295M (2002)

2. Ma D., Rajakumaraswamy N., Maze M.: α2-Adrenoceptor agonists: shedding light on neuroprotection? Br. Med. Bull. 71: 77-92 (2004)

3. Karkoulias G., Flordellis C.: Delayed transactivation of the receptor for nerve growth factor is required for sustained signaling and differentiation by α2-Adrenergic receptors in transfected PC12 cells. Cell. Signal. 19: 945-957 (2007)

4. Lonze B.E., Ginty D.D.: Function and regulation of CREB family transcription factors in the nervous system. Neuron 35: 605-623 (2002)

5. Karkoulias G., Mastrogianni O., Papathanasopoulos P., Paris H., Flordellis C.: a2-Adrenergic receptors activate CREB through arachidonic acid metabolism and protein kinase A in a subtype-specific manner, J. Neurochem. 103: 882-895 (2007)

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