Oxidative stress induces diacylglycerol-generating pathways in rat cerebral cortex synaptic endings

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

Rosario

Congreso; XLII reuni¨®n anual de la SAIB; 2006

SAIB

Oxidative stress induces diacylglycerol-generating pathways in rat cerebral cortex synaptic endings. Mateos, Melina V; Uranga, Romina M; Salvador, Gabriela A; Giusto, Norma M. Instituto de Investigaciones Bioqu¨ªmicas de Bah¨ªa Blanca (INIBIBB), B8000FWB, Bah¨ªa Blanca, ARGENTINA. E-mail: mvmateos@criba.edu.ar   Neurotoxic agents such as Fe2+ induce lipid peroxidation, impairment of glutamate and glucose transport and mitochondrial dysfunction. These toxic effects on biological membranes are comparable to those of ¦Â amyloid peptide (¦ÂA) on the brain of Alzheimer¡¯s disease patients. Recent studies from our laboratory demonstrated that the exposure of rat cerebral cortex synaptic endings (Syn) to Fe2+ induces a marked increase in tyrosine phosphorylation of several proteins and the activation of PI3K/Akt pathway. Our purpose was to study the effect of oxidative insult on diacylglycerol (DAG) generation from phosphatidylcholine (PC) in Syn. DAG from PC can be generated by phospholipase D (PLD) and phosphatidic acid phosphohydrolase type 2 (PAP2) pathway or by a phosphatidylcholine-specific phospholipase C (PC-PLC). Free iron stimulated DAG generation from PC as a time-function. Assays conducted with ethanol demonstrated that both PLD/PAP2 and PLC pathways were stimulated by Fe2+. Preincubation of Syn either with the specific PI3K inhibitor (LY294002) or with Genistein or Herbimycin A, two tyrosine kinases inhibitors, did not modify the DAG increase induced by Fe2+. This work constitutes the first report about the effect of oxidative insult on DAG generating pathways in synaptic endings. DAG formation induced by Fe2+ seems to be independent of PI3K activity and tyrosine phosphorylation pathways.