Autor |
Carnevalli, Larissa S.
![]() ![]() Pereira, Catia M. ![]() ![]() Jaqueta, Carolina B. ![]() ![]() Alves, Viviane S. ![]() ![]() Paiva, Vanessa N. ![]() ![]() Vattem, Khrishna M. ![]() Wek, Ronald C. ![]() Mello, Luiz Eugenio Araujo de Moraes ![]() ![]() Castilho, Beatriz A. ![]() ![]() |
Instituição | Universidade Federal de São Paulo (UNIFESP) Indiana Univ |
Resumo | In response to different cellular stresses, a family of protein kinases phosphorylates eIF2 alpha (alpha subunit of eukaryotic initiation factor-2), contributing to regulation of both general and gene-specific translation proposed to alleviate cellular injury or alternatively induce apoptosis. Recently, we reported eIF2 alpha(P) (phosphorylated eIF2 alpha) in the brain during SE (status epilepticus) induced by pilocarpine in mice, an animal model of TLE (temporal lobe epilepsy) [Carnevalli, Pereira, Longo, Jaqueta, Avedissian, Mello and Castilho (2004) Neurosci. Lett. 357, 19 1 194]. We show in the present study that one eIF2 alpha kinase family member, PKR (double-stranded-RNA-dependent protein kinase), is activated in the cortex and hippocampus at 30 min of SE, reflecting the levels of eIF2 alpha(P) in these areas. in PKR-deficient animals subjected to SE, eIF2 alpha phosphorylation was clearly evident coincident with activation of a secondary eIF2 alpha kinase, PEK/PERK (pancreatic eIF2 alpha kinase/RNA-dependent-protein-kinase-like endoplasmic reticulum kinase), denoting a compensatory mechanism between the two kinases. the extent of eIF2 alpha phosphorylation correlated with the inhibition of protein synthesis in the brain, as determined from polysome profiles. We also found that C57BL/6 mice, which enter SE upon pilocarpine administration but are more resistant to seizure-induced neuronal degeneration, showed very low levels of eIF2 alpha(P) and no inhibition of protein synthesis during SE. These results taken together suggest that PKR-mediated phosphorylation of eIF2 alpha contributes to inhibition of protein synthesis in the brain during SE and that sustained high levels of eIF2 alpha phosphorylation may facilitate ensuing cell death in the most affected areas of the brain in TLE. |
Assunto |
double-stranded-RNA-dependent protein kinase (PKR)
pilocarpine status epilepticus alpha subunit of eukaryotic initiation factor-2 (eIF2 alpha) temporal lobe epilepsy model translation initiation |
Idioma | Inglês |
Data | 2006-07-01 |
Publicado em | Biochemical Journal. London: Portland Press Ltd, v. 397, p. 187-194, 2006. |
ISSN | 0264-6021 (Sherpa/Romeo, fator de impacto) |
Editor | Portland Press Ltd |
Extensão | 187-194 |
Fonte |
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Direito de acesso | Acesso aberto ![]() |
Tipo | Artigo |
Web of Science | WOS:000238699200021 |
URI | http://repositorio.unifesp.br/handle/11600/28987 |
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