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

BackgroundArachidonic acid is released from cellular membranes by the action of phospholipase A2 (PLA2) and is implicated in microtubule-associated protein Tau phosphorylation. Tau hyperphosphorylation affects its ability to stabilize microtubules.ObjectiveTo determine the effect of PLA2 inhibition on the phosphorylation state of Tau phosphoepitopes in primary cultures of hippocampal neurons.Methods4 DIC neurons were incubated at different concentrations of methyl-arachidonylfluorophosphonate (MAFP), an irreversible inhibitor of cPLA2 and iPLA2. 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).ResultsThe Ser214 site was hyperphosphorylated upon MAFP treatment. Significant differences were observed with 10 μM (p=0.01), 50 μM (p=0.01) and 100 μM (p=0.05) of MAFP. Less-intense changes were found in other phosphoepitopes.ConclusionThe present findings indicate that the phosphorylation of Ser214 is regulated by c- and/or iPLA2, whereas other phosphoepitopes primarily regulated by GKS3b were not affected.