Oxidative stress induced by free iron stimulates phosphatidylcholine breakdown in cerebral cortex synaptic endings

MATEOS MELINA; SALVADOR GABRIELA; GIUSTO NORMA

San Diego USA

Congreso; Experimental Biology Annual Meeting; 2008

American Society For Biochemistry and Molecular Biology

Oxidative stress induced by free iron stimulates phosphatidylcholine breakdown in cerebral cortex synaptic endings Mateos, Melina V; 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 Neuronal damage induced by transition metal ions is comparable with the toxic effect of ¦Â amyloid peptide. Our purpose was to study the effect of oxidative insult on diacylglycerol (DAG) generation from phosphatidylcholine (PC) in rat cerebral cortex synaptosomes. DAG from PC can be generated by phospholipase D (PLD) and phosphatidic acid phosphatase 2 pathway or by a phosphatidylcholine-specific phospholipase C (PC-PLC). Oxidative injury induced by FeSO4 increased DAG generation by 77% with respect to control conditions. Experiments carried out in the presence of ethanol, demonstrated that both PLD and PC-PLC pathways contributed to DAG generation in the presence of iron. Additionally, free fatty acid generation was inhibited in the presence of Fe2+. Neither the specific phosphoinositide-3-kinase inhibitor (LY294002) nor Herbimycin A modified the DAG increase induced by Fe2+. Assays conducted with Fe2+ and either DAG lipase or DAG kinase inhibitors, showed no differences in  DAG levels. The phosphoinositide-PLC inhibitor, U73122, inhibited DAG formation by 23% after 60 min of iron exposure. Our results demonstrate that the generation of lipid messengers through PC breakdown is activated under oxidative injury conditions in synaptic endings. Supported by Consejo Nacional de Investigaciones Cient¨ªficas y T¨¦cnicas, Universidad Nacional del Sur and Agencia Nacional de Promoci¨®n Cient¨ªfica y Tecnol¨®gica.