APOPTOSIS INDUCTION THROUGHOUT ACTIVATION OF ANG II AT2 RECEPTOR

MANZUR MJ, BERÓN W, CIUFFO GM

Carlos Paz, Cordoba-Argentina

Congreso; Sociedad Argentina de Investigación Bioquímica y Biología Molecular-SAIB; 2008

Angiotensin II (Ang II) receptor expression is highly modulated during development, suggesting a role of these receptors in growth and organogenesis. AT2 receptors are abundantly expressed in fetal tissues, where they probably contribute to development. However, the detailed mechanism is unclear. Here we report the induction of apoptosis via AT2 receptor signaling, as a primary mechanism of tissue differentiation. To study the interaction between AT1 and AT2 receptors we design a co-transfection experiment to express both receptors in Hela cells. Receptors do not colocalize even after stimulation. In cells transfected with AT2 receptors and stimulated with Ang II [10-7] for different times, apoptosis appeared after 30 min stimulation. Cells were analyzed by immunofluorescence staining and confocal microscopy. We identified apoptotic cells by actin cytoskeleton depolymerization and chromatin condensation. Co-transfection with RhoA suggest a potential participation of this GTPase protein in the process. After quantification of apoptotic cells, the effect was statistically significant at 30, 60 to 240 min of stimulation. The present results showed no physical interaction between Ang II AT1 and AT2 receptors. On the other hand, AT2 receptor stimulation induces apoptosis, evaluated at different levels in a time-dependent manner.