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Oxidative Stress Induced by Free Iron Stimulates Phosphatidylcholine Breakdown in Cerebral Cortex Synaptic Endings
Author(s) -
Mateos Melina Valeria,
Salvador Gabriela Alejandra,
Giusto Norma Maria
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.805.3
Subject(s) - diacylglycerol kinase , phosphatidic acid , chemistry , phospholipase c , oxidative stress , phosphatidylcholine , biochemistry , diacylglycerol lipase , oxidative phosphorylation , kinase , protein kinase c , signal transduction , phospholipid , membrane
Neuronal damage induced by transition metal ions is comparable with the toxic effect of β 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 FeSO 4 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 Fe 2+ . Neither the specific phosphoinositide‐3‐kinase inhibitor (LY294002) nor Herbimycin A modified the DAG increase induced by Fe 2+ . Assays conducted with Fe 2+ 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 Científicas y Técnicas, Universidad Nacional del Sur and Agencia Nacional de Promoción Científica y Tecnológica .