BACKGROUND: 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. OBJECTIVE: To determine the effect of PLA(2) inhibition on the phosphorylation state of Tau phosphoepitopes in primary cultures of hippocampal neurons. METHODS: 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). RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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. OBJECTIVE: To determine the effect of PLA(2) inhibition on the phosphorylation state of Tau phosphoepitopes in primary cultures of hippocampal neurons. METHODS: 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). RESULTS: 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. CONCLUSION: 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.
Authors: L L Talib; S R Hototian; H P G Joaquim; O V Forlenza; W F Gattaz Journal: Eur Arch Psychiatry Clin Neurosci Date: 2015-04-29 Impact factor: 5.270
Authors: Evelin L Schaeffer; Vanessa J De-Paula; Emanuelle R da Silva; Barbara de A Novaes; Heni D Skaf; Orestes V Forlenza; Wagner F Gattaz Journal: J Neural Transm (Vienna) Date: 2011-03-09 Impact factor: 3.575