Inhibition of phospholipase A(2) in rat brain decreases the levels of total Tau protein

Autor(es)

Schaeffer, Evelin L. ^{[1, 2]} ; De-Paula, Vanessa J. ^{[1, 2]} ; da Silva, Emanuelle R. ^{[1, 2]} ; Novaes, Barbara de A. ^{[1, 2]} ; Skaf, Heni D. ^{[1, 2]} ; Forlenza, Orestes V. ^{[1, 2]} ; Gattaz, Wagner F. ^{[1, 2]}

Afiliação do(s) autor(es)

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

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

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF NEURAL TRANSMISSION; v. 118, n. 9, p. 1273-1279, SEP 2011.
• Citações Web of Science: 15

Resumo

The microtubule-associated protein Tau promotes the assembly and stability of microtubules in neuronal cells. Six Tau isoforms are expressed in adult human brain. All six isoforms become abnormally hyperphosphorylated and form neurofibrillary tangles in Alzheimer disease (AD) brains. In AD, reduced activity of phospholipase A(2) (PLA(2)), specifically of calcium-dependent cytosolic PLA(2) (cPLA(2)) and calcium-independent intracellular PLA(2) (iPLA(2)), was reported in the cerebral cortex and hippocampus, which positively correlated with the density of neurofibrillary tangles. We previously demonstrated that treatment of cultured neurons with a dual cPLA(2) and iPLA(2) inhibitor, methyl arachidonyl fluorophosphonate (MAFP), decreased total Tau levels and increased Tau phosphorylation at Ser(214) site. The aim of this study was to conduct a preliminary investigation into the effects of in vivo infusion of MAFP into rat brain on PLA(2) activity and total Tau levels in the postmortem frontal cortex and dorsal hippocampus. PLA(2) activity was measured by radioenzymatic assay and Tau levels were determined by Western blotting using the anti-Tau 6 isoforms antibody. MAFP significantly inhibited PLA(2) activity in the frontal cortex and hippocampus. The reactivity to the antibody revealed three Tau protein bands with apparent molecular weight of close to 40, 43 and 46 kDa in both brain areas. MAFP decreased the 46 kDa band intensity in the frontal cortex, and the 43 and 46 kDa band intensities in the hippocampus. The results indicate that in vivo PLA(2) inhibition in rat brain decreases the levels of total (nonphosphorylated plus phosphorylated) Tau protein and corroborate our previous in vitro findings. (AU)

• Processo FAPESP: 04/14516-0 - Inibição da Fosfolipase A2 no hipocampo de ratos e seus efeitos diferenciais na fluidez de membranas plasmáticas e nucleares: possíveis correlações com a memória?
• Beneficiário: Wagner Farid Gattaz
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 02/13633-7 - Metabolismo de fosfolípides em doenças neuropsiquiátricas
• Beneficiário: Wagner Farid Gattaz
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 08/09861-0 - Efeitos da inibição crônica da fosfolipase A2 sobre a fluidez de membranas e a clivagem da proteína precursora de amilóide no córtex pré-frontal e hipocampo dorsal de ratos
• Beneficiário: Heni Debs Skaf
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 08/09494-8 - Efeitos da inibição crônica da Fosfolipase A2 sobre a fluidez de membranas e a clivagem da proteína precursora de amilóide no córtex pré-frontal e hipocampo dorsal de ratos
• Beneficiário: Emanuelle Roberta da Silva
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica