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Inhibition of phospholipase A2 increases Tau phosphorylation at Ser214 in embryonic rat hippocampal neurons
Authors:Vanessa J De-Paula  Evelin L Schaeffer  Leda L Talib  Wagner F Gattaz  Orestes V Forlenza
Institution:1. National Institute of Science and Technology in Molecular Medicine, Federal University of Minas Gerais(UFMG), Brazil;2. Department of Physical Education, Federal University of Viçosa, Minas Gerais, Brazil;3. Department of Mental Health, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;4. Department of Pediatrics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;1. Department of Emergency Medicine, Gaziantep University School of Medicine, Gaziantep, Turkey;2. Department of Emergency Medicine, 25 Aralik State Hospital, Gaziantep, Turkey;3. Department of Medical Biochemistry, Gaziantep University School of Medicine, Gaziantep, Turkey;4. Department of Biochemistry, Akçakale State Hospital, Sanl?urfa, Turkey;1. Institut d''Investigacions Biomèdiques de Barcelona (IIBB), CSIC, Barcelona, Spain;2. Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland;3. Institut d''Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain;4. Alzheimer''s Disease and Other Cognitive Disorders Unit, Department of Neurology, Hospital Clínic, Barcelona, Spain;5. Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain;1. Pós-graduação em Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Paraná, 80215-901, Curitiba, Paraná, Brazil;2. Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil;1. Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA;2. Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA
Abstract: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.
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