Synaptic PKC is a downstream effector of PLD during iron-induced oxidative stress. Effect of aging

MATEOS, MELINA; GIUSTO, NORMA; SALVADOR, GABRIELA ALEJANDRA

Congreso; SAIB: Molecular mechanisms in cell signaling and gene expression; 2013

We have previously demonstrated that iron-induced oxidative stress activates phospholipase D (PLD) signaling in cerebral cortex synaptic endings (Syn). The purpose of this work was to study the PLD downstream signaling events  during iron-induced oxidative stress in Syn obtained from adult (4 months old) and aged (28 months old) rats. Diacylglycerol (DAG) production was increased in Syn from adult rats exposed to iron. This rise in DAG formation was dependent on PLD1 and PLD2 activities. Western blot assays showed that iron overload activates synaptic PKCalpha/betaII and PKD1 and reduces glutamate uptake, both in adult and aged rats. In adult rats, PLD1 and PLD2 modulated PKCalpha/betaII and PKD1 activation. In contrast, in senile rats, DAG formation catalyzed by PLDs did not participate in PKD1 and PKCalpha/betaII activation, but it was dependent on PKC activities. Moreover, PLD1 and PKC inhibition (with 0.15 microM EVJ and 10 microM BIM, respectively) restored glutamate uptake to control levels only in Syn from aged rats. On the contrary, PLD2 inhibition (with 0.5 microM APV) reduced even more the uptake of glutamate in adult and aged Syn. Our results show a differential regulation of PKCalpha/betaII and PKD1 by PLDs during iron-induced oxidative stress as a consequence of aging.