Cellular and Molecular Neurobiology
Author: Helga Myrna Blanco | Email: helgamyrna@gmail.com
Helga Myrna Blanco 1°, Maria Elena Arce 1°, Claudia Banchio 2°, Sergio Eduardo Alvarez 1°, Gladys Maria Ciuffo 1°
1° IMIBIO CONICET. UNSL. San Luis – Argentina
2° IBR CONICET. Rosario – Argentina
We explored neurite outgrowth induced by Ang II AT2 receptors and the participation of different signaling pathways. Previously, we demonstrated that AT2 receptors induced neurite outgrowth in neuroblastoma cell lines, Neuro2A and SH-SY5Y. We used specific inhibitors to enlighten the role of different signaling in neurite outgrowth. SH-SY5Y cells were pretreated with the inhibitors, stimulated with CGP42112 and allowed to differentiate (3 days). Cells exhibiting at least one neurite longer that a cell body showed a 2-fold increase when stimulated with Ang II or CGP42112. Similar results were observed in cells with 2 or more neurites. Our results suggest that PI3K is not important in AT2R-induced neurite outgrowth. On the contrary, inhibition of MEK/ERK, SphK1 and c-Src pathways prevented neurite outgrowth induced by CGP42112. CGP42112 stimulated a rapid and transient (30 sec) phosphorylation of c-Src at residue Y416 (indicative of activation), following by a Src deactivation as indicated by phosphorylation of Y527. In summary, we demonstrated that AT2R-stimulated neurite outgrowth in SH-SY5Y cells involves participation of MEK, SphK and c-Src and suggests a possible transactivation of TrkA. AT2 signaling pathway is a key player in neuronal differentiation and might be a potential target for therapeutic treatments.