PLD and PI3K signaling in neuronal oxidative stress

SALVADOR, G

Mar del Plata

Conferencia; LI Reunion Anual de SAIB; 2015

SAIB

LI-01PLD AND PI3K SIGNALING IN NEURONAL OXIDATIVE STRESSSalvador, GAINIBIBB-UNS-CONICET. Bahia Blanca-ArgentinaLipid signaling cascades have important roles in the regulation of cellular fate. Our studies provide new insights intothe regulation and physiological role of lipid messengers during neuronal oxidative stress (OS). Specifically, we havestudied neuronal signal events derived from phosphatidylcholine (PC) and phosphatidylinositol (PI).Synaptic OS triggers phospholipase D (PLD) activation and, consequently, a rise in phosphatidic acid anddiacylglycerol (DAG) generation from PC. These lipid messengers activate downstream signaling cascades asERK1/2 and conventional PKCs and regulate glutamate transport in the synaptic cleft of adult rat brains. Studies inaged brains reveal an increased synaptic susceptibility to OS and an impairment in the DAG-mediated signalingpathways. Tyrosine phosphorylation associated with PI phosphorylation and phosphoinositide 3 kinase (PI3K)activation are stimulated in OS-exposed hippocampal neurons and synapses. PI3K activation and its downstreameffector kinase, Akt, trigger pleiotropic neuroprotective mechanisms against OS by suppressing FOXO3Atranscriptional activity, inhibiting GSK3β and upregulating glutathione metabolism.In summary, we have characterized signaling events elicited by PLD and PI3K activation, which produce lipidmessengers that control smart strategies for preventing neuronal death triggered by OS