Angiotensin II AT2 receptors induced neurite outgrowth by transactivation of Nerve Growth Factors TrkA receptor.

BLANCO H; ALVAREZ SE; CIUFFO GM

Mendoza

Congreso; XXXI Reunión Anual de la Sociedad de Biología de Cuyo; 2013

The sprouting of neurites are key morphological features characterizing neuronal differentiation. Angiotensin II (Ang II) elicits a variety of biological effects through specific receptors AT1 and AT2, present in well-identified nuclei in the brain. The potential effect of Ang II on neuronal differentiation was suggested by our group previously. Thus, we decided to examine the role of Ang II and CGP42112, an specific AT2 receptor agonist, in neuronal differentiation by using SH-SY5Y human neuroblastoma cells. Here, we show that treatment for 3 days with either Ang II (100 nM) or CGP42112 (10 nM) induce neurite sprouting, as analyzed by optic microscopy (15?20 random fields were counted). Cells showing at least one neurite with a twofold length than the soma diameter were considered as differentiated. Neuronal differentiation was also assessed by the increase in the expression of Beta III tubulin, a neuritogenesis marker. Both Ang II and GCP4212-induced neurite outgrowth were abolished in cells pretreated with AG879, a specific TrkA nerve growth factor (NGF) receptor antagonist or PP2, a c-Src family protein inhibitor. These results suggest that activation of c-Src, and transactivation of TrkA receptor for Ang II or CGP42112 are important for neuronal differentiation.