Involvement of c-Src kinase in neuronal differentiation mediated by Angiotensin II AT2 receptors.

BLANCO H; CIUFFO GM; ALVAREZ SE

Mendoza

Congreso; 48th Reunión Científica Anual de SAIB; 2012

Angiotensin II (Ang II), the active peptide of the renin?angiotensin system, elicits a variety of biological effects through specific receptors, AT1 and AT2.  Although AT2 receptors may be involved in neuronal differentiation, the mechanism is not well defined. Thus, we decided to examine the role of Ang II and the AT2 specific receptor agonist, CGP42112, in differentiation of SHsy5y neuroblastoma cells. The expression of AT1 and AT2 receptors was determined by western blot (WB). CGP42112 induced differentiation and increased the expression of βIII tubulin, a neuritogenesis marker as assessed by optic microscopy and WB respectively. Since nerve growth factor (NGF) induces neuronal differentiation through ERK1/2 activation, we studied the involvement of this pathway in the process. While treatment for 3 days with Ang II or CGP42112 caused a decrease in ERK1/2 phosphorylation, pre-incubation with UO126, MEK1/2 inhibitor, did not affect differentiation. Previously, we have shown that activation of AT2 receptor induced tyrosine kinase c-Src activation/phosphorylation. Therefore, we examined its contribution to neurite outgrowth process. Interestingly, the neuritogenesis induced by CGP42112 was abolished by PP2, a c-Src inhibitor. Altogether, these results suggest that activation of c-Src, but not ERK1/2, is important for neuronal differentiation mediated by AT2 receptors in SHsy5y cells.