Distinctive roles of PLD signaling elicited by oxidative stress in synaptic endings from adult and aged rats

MATEOS, M.; GIUSTO, N.; SALVADOR, G. AUTOR CORRESP.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2012 vol. 1823 p. 2136 - 2148

0167-4889

Iron-induced oxidative stress has been proposed as one of the main contributors to neuronal damage in several neurodegenerative disorders such as Alzheimer?s and Parkinson?s disease. The role of iron in oxidative injury and in the triggering of cannonical signaling pathways has been extensively described; however, little is known about the role of lipid signal transduction in neurodegeneration.  The purpose of this work was to characterize the regulation and the crosstalk between phosphatidylcholine (PC)-derived diacylglycerol (DAG) and cannonical signaling pathways during iron-induced oxidative stress in cerebral cortex synaptic endings (Syn) obtained from adult (4 month old) and aged (28 month old) rats.  DAG production was increased in Syn exposed to iron. This rise in DAG formation was due to phospholipase D1 (PLD1) and PLD2 activation. In adult rats, PKD1, ERK1/2 and PKCá/âII activation was PLD1 and PLD2 dependent. On the contrary, in senile rats, DAG formation catalyzed by PLDs did not participate in PKD1, ERK1/2 and PKCá/âII regulation, but it was dependent on ERK and PKC activities. Iron-induced oxidative stress promoted an increased localization of PLD1 in membrane rafts, whereas PLD2 was excluded from these domains and appeared to be involved in glutamate transporter function. Our results show a differential regulation and synaptic function of DAG generated by PLDs during iron-induced oxidative stress as a consequence of aging.