Inhibition of phospholipase A(2) increases Tau phosphorylation at Ser214 in embryonic rat hippocampal neurons

Autor(es)

De-Paula, Vanessa J. ^[1] ; Schaeffer, Evelin L. ^[1] ; Talib, Leda L. ^[1] ; Gattaz, Wagner F. ^[1] ; Forlenza, Orestes V. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Psychiat, Fac Med, Neurosci Lab, LIM 27, BR-05403010 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Psychiat, Fac Med, Neurosci Lab, LIM 27, IPq HCFMUSP, BR-05403010 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS; v. 82, n. 1, p. 57-60, JAN 2010.
• Citações Web of Science: 10

Resumo

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 mu M (p = 0.01), 50 mu M (p = 0.01) and 100 mu M (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. (C) 2009 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 02/13633-7 - Metabolismo de fosfolípides em doenças neuropsiquiátricas
• Beneficiário: Wagner Farid Gattaz
• Modalidade de apoio: Auxílio à Pesquisa - Temático