Inhibition of phospholipase A2 increases tau phosphorylation at Ser214 in embryonic rat hippocampal neurons.

Vanessa J De-Paula, Evelin L Schaeffer, Leda L Talib, Wagner F Gattaz, Orestes V Forlenza

Laboratory of Neuroscience LIM-27, Department and Institute of Psychiatry, Faculty of Medicine, University of Sao Paulo, Brazil.

Prostaglandins, leukotrienes, and essential fatty acids 2010 Jan

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Arachidonic acid is released from cellular membranes by the action of phospholipase A(2) (PLA(2)) and is implicated in microtubule-associated protein Tau phosphorylation. Tau hyperphosphorylation affects its ability to stabilize microtubules. To determine the effect of PLA(2) inhibition on the phosphorylation state of Tau phosphoepitopes in primary cultures of hippocampal neurons. 4 DIC neurons were incubated at different concentrations of methyl-arachidonylfluorophosphonate (MAFP), an irreversible inhibitor of cPLA(2) and iPLA(2). Changes on Tau phosphorylation were determined by Western blotting with a panel of anti-Tau antibodies (C-terminal, Ser199/202, Ser202/205, Ser396 and Ser214). The Ser214 site was hyperphosphorylated upon MAFP treatment. Significant differences were observed with 10 microM (p=0.01), 50 microM (p=0.01) and 100 microM (p=0.05) of MAFP. Less-intense changes were found in other phosphoepitopes. The present findings indicate that the phosphorylation of Ser214 is regulated by c- and/or iPLA(2), whereas other phosphoepitopes primarily regulated by GKS3b were not affected. Copyright 2009 Elsevier Ltd. All rights reserved.

Citation

Vanessa J De-Paula, Evelin L Schaeffer, Leda L Talib, Wagner F Gattaz, Orestes V Forlenza. Inhibition of phospholipase A2 increases tau phosphorylation at Ser214 in embryonic rat hippocampal neurons. Prostaglandins, leukotrienes, and essential fatty acids. 2010 Jan;82(1):57-60