ANGIOTENSIN II AT RECEPTORS MODULATE NEURONAL DIFFERENTIATION

BLANCO HM; BANCHIO C; CIUFFO, GM; ALVAREZ, SE

Potrero de los Funes

Congreso; XLVI reunión anual de SAIB- Potrero de los Funes; 2011

Soc. Arg. de Invest. Bioqca. y Biol. Molecular

Neuronal differentiation is a complex process characterized by neurite outgrowth. Binding of nerve growth factor (NGF) to the receptor TrKA induces differentiation by activating ERK pathway. In the past years it has become clear that, in addition to its cardiovascular roles, the octapeptide Angiotensin II (Ang II) has many functions in the brain by acting through two receptor subtypes, AT and AT . However its role in neuronal differentiation is not well 1 2 defined. Thus, we decided to examine the participation of Ang II and NGF in differentiation of Neuro2A cells with special focus in ERK activation. By RT-PCR and western blot we determined that Neuro2A cells express AT , AT and TrKA receptors. Cells were 1 2 stimulated with Ang II, CGP42112 (AT specific receptor agonist) or 2 NGF and active ERK detected in cell lysates by western blot with specific antibodies. As expected, NGF induces ERK phosphorylation in a time dependent manner. Likewise, Ang II and CGP42112 stimulate ERK, suggesting an AT receptor-dependent 2 effect. To study differentiation, cells were treated with agonists for 24 h and observed under optic and fluorescent microscopy. Both Ang II and CGP42112 induce differentiation and expression of ßIII tubulin, a neuritogenesis marker. These results suggest that AT 2 receptor activation induces ERK phosphorylation, expression of ßIII tubulin and differentiation in Neuro2A cells.