Cellular and Molecular Neurobiology
Author: Maria Elena Arce | email: earce.arce7@gmail.com
Helga Myrna Blanco 1°, Celia N. Perez 1°, Claudia Banchio 2°, Sergio Eduardo Alvarez 1°, Maria Elena Arce 1°, Gladys Maria Ciuffo 1°
1° IMIBIO-SL CONICET. Univ. Nacional de San Luis. San Luis, Argentina.
2° IBR- CONICET. Rosario, Argentina
It is well known that neurite outgrowth could be induced by Angiotensin II (Ang II) AT2 receptors; however, the signaling pathways that link AT2 receptor activation with neurite outgrowth remain unclear. Neural differentiation and protection induced by AT2 receptors also involves the activation of NGF (nerve growth factor). Certainly, Ang II stimulates the receptor tyrosine kinase A (TrkA) phosphorylation. Moreover, it has also been shown that NGF-induced neurite extension requires the activation of sphingosine kinase 1(SphK1). We showed that Ang II and CGP42112A (AT2 receptor agonist) promote neuronal differentiation by inducing neurite outgrowth in SH-SY5Y neuroblastoma cells. Then, we explored the participation of three different pathways in the neurite outgrowth induced by Ang II or CGP42112A by using specific inhibitors of c-Src (PP2), MEK (UO126), TrkA (AG879) and SphK (SKI-II). We conclude that stimulation of Ang II AT2 receptors induce neurite outgrowth in SH-SY5Y cells through a signaling mechanism that involves MEK/ERK,SphK and c-Src and provide evidence for a possible involvement of TrkA receptors in the pathway.