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Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways

Almeida, R D ; Manadas, B J ; Melo, C V ; Gomes, J R ; Mendes, C S ; Grãos, M M ; Carvalho, R F ; Carvalho, A P ; Duarte, C B

Cell death and differentiation, 2005-10, Vol.12 (10), p.1329-1343 [Revista revisada por pares]

England: Nature Publishing Group

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Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways
Autor: Almeida, R D ; Manadas, B J ; Melo, C V ; Gomes, J R ; Mendes, C S ; Grãos, M M ; Carvalho, R F ; Carvalho, A P ; Duarte, C B
Materias: Animals ; Apoptosis - drug effects ; Apoptosis - physiology ; Brain-Derived Neurotrophic Factor - pharmacology ; Caspase 3 ; Caspases - biosynthesis ; Cell death ; Cell Survival ; Down-Regulation - drug effects ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Glutamic Acid - toxicity ; Hippocampus - cytology ; Hippocampus - drug effects ; Hippocampus - enzymology ; Hippocampus - metabolism ; MAP Kinase Signaling System - drug effects ; MAP Kinase Signaling System - physiology ; Neurons - cytology ; Neurons - drug effects ; Neurons - enzymology ; Neurons - metabolism ; Neuroprotective Agents - pharmacology ; Phosphatidylinositol 3-Kinases - metabolism ; Protein-Serine-Threonine Kinases - metabolism ; Proto-Oncogene Proteins - metabolism ; Proto-Oncogene Proteins c-akt ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; ras Proteins - metabolism ; Rats ; Rats, Wistar ; Transfection
Es parte de: Cell death and differentiation, 2005-10, Vol.12 (10), p.1329-1343
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descripción: Neurotrophins protect neurons against glutamate excitotoxicity, but the signaling mechanisms have not been fully elucidated. We studied the role of the phosphatidylinositol 3-kinase (PI3-K) and Ras/mitogen-activated protein kinase (MAPK) pathways in the protection of cultured hippocampal neurons from glutamate induced apoptotic cell death, characterized by nuclear condensation and activation of caspase-3-like enzymes. Pre-incubation with the neurotrophin brain-derived neurotrophic factor (BDNF), for 24 h, reduced glutamate-evoked apoptotic morphology and caspase-3-like activity, and transiently increased the activity of the PI3-K and of the Ras/MAPK pathways. Inhibition of the PI3-K and of the Ras/MAPK signaling pathways abrogated the protective effect of BDNF against glutamate-induced neuronal death and similar effects were observed upon inhibition of protein synthesis. Moreover, incubation of hippocampal neurons with BDNF, for 24 h, increased Bcl-2 protein levels. The results indicate that the protective effect of BDNF in hippocampal neurons against glutamate toxicity is mediated by the PI3-K and the Ras/MAPK signaling pathways, and involves a long-term change in protein synthesis.
Editor: England: Nature Publishing Group
Idioma: Inglés

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Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways

Almeida, R D ; Manadas, B J ; Melo, C V ; Gomes, J R ; Mendes, C S ; Grãos, M M ; Carvalho, R F ; Carvalho, A P ; Duarte, C B

England: Nature Publishing Group

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