“Insulin and IGF-1 signaling involves PI3K activation in cerebral cortex synaptic endings

URANGA, ROMINA; MATEOS ; MELINA; GIUSTO, NORMA; SALVADOR, GABRIELA

Pinamar

Congreso; 10th Congress PABMB, 41st Annual Meeting SAIB and 20th Annual Meeting SAN.; 2005

SAIB, SAN; PABMS

INSULIN AND IGF-1 SIGNALING INVOLVES PI·3K ACTIVATION IN CEREBRAL CORTEX SYNAPTIC ENDINGS. Uranga RM; Mateos, MV; Giusto N; Salvador GA. Instituto de Investigaciones Bioquímicas de Bahía Blanca, B8000FWB, Bahía Blanca, ARGENTINA. E-mail: ruranga@criba.edu.ar. Phosphatidylinositol 3-kinase (PI3K) phosphorylates the 3’OH position of the inositol ring of phosphoinositides. PI3K signaling is activated by a variety of extracellular stimuli and has been implicated in a wide range of cellular processes including cell cycle progression, cell growth, cell motility, cell adhesion and cell survival. We have previously demonstrated the presence of PI3K and its activation under oxidative stress conditions in cerebral cortex synaptic endings. The goal of this work was to study the involvement of PI3K in neurotrophic factor action in the synaptic terminal. For this purpose we evaluated the phosphorylation of poliphosphoinositides in synaptosomes incubated in the presence of either insulin (175nM) or IGF-1(15nM) and 5 mCi [g-32P]ATP. Insulin increased phosphatidylinositolmonophosphate (PIP) levels by 80% with respect to control conditions at 5 min incubation. On the other hand, IGF-1 stimulated PI kinase by 187% compared to the control. LY294002, a selective PI3K inhibitor, abolished PI kinase activation. Additionally, we demonstrated that both growth factors were able to increase Akt phosphorylation at serine 473 position. Our results demonstrate the involvement of PI3K/Akt pathway in insulin and IGF-1 signaling cascade in cerebral cortex synapses. Phosphatidylinositol 3-kinase (PI3K) phosphorylates the 3’OH position of the inositol ring of phosphoinositides. PI3K signaling is activated by a variety of extracellular stimuli and has been implicated in a wide range of cellular processes including cell cycle progression, cell growth, cell motility, cell adhesion and cell survival. We have previously demonstrated the presence of PI3K and its activation under oxidative stress conditions in cerebral cortex synaptic endings. The goal of this work was to study the involvement of PI3K in neurotrophic factor action in the synaptic terminal. For this purpose we evaluated the phosphorylation of poliphosphoinositides in synaptosomes incubated in the presence of either insulin (175nM) or IGF-1(15nM) and 5 mCi [g-32P]ATP. Insulin increased phosphatidylinositolmonophosphate (PIP) levels by 80% with respect to control conditions at 5 min incubation. On the other hand, IGF-1 stimulated PI kinase by 187% compared to the control. LY294002, a selective PI3K inhibitor, abolished PI kinase activation. Additionally, we demonstrated that both growth factors were able to increase Akt phosphorylation at serine 473 position. Our results demonstrate the involvement of PI3K/Akt pathway in insulin and IGF-1 signaling cascade in cerebral cortex synapses.