Phosphorylation of the ot subunit of translation initiation factor-2 by PKR mediates protein synthesis inhibition in the mouse brain during status epilepticus

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dc.contributor.author Carnevalli, Larissa S. [UNIFESP]
dc.contributor.author Pereira, Catia M. [UNIFESP]
dc.contributor.author Jaqueta, Carolina B. [UNIFESP]
dc.contributor.author Alves, Viviane S. [UNIFESP]
dc.contributor.author Paiva, Vanessa N. [UNIFESP]
dc.contributor.author Vattem, Khrishna M.
dc.contributor.author Wek, Ronald C.
dc.contributor.author Mello, Luiz Eugenio Araujo de Moraes [UNIFESP]
dc.contributor.author Castilho, Beatriz A. [UNIFESP]
dc.date.accessioned 2016-01-24T12:41:16Z
dc.date.available 2016-01-24T12:41:16Z
dc.date.issued 2006-07-01
dc.identifier http://dx.doi.org/10.1042/BJ20051643
dc.identifier.citation Biochemical Journal. London: Portland Press Ltd, v. 397, p. 187-194, 2006.
dc.identifier.issn 0264-6021
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/28987
dc.description.abstract 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. en
dc.format.extent 187-194
dc.language.iso eng
dc.publisher Portland Press Ltd
dc.relation.ispartof Biochemical Journal
dc.rights Acesso aberto
dc.subject double-stranded-RNA-dependent protein kinase (PKR) en
dc.subject pilocarpine en
dc.subject status epilepticus en
dc.subject alpha subunit of eukaryotic initiation factor-2 (eIF2 alpha) en
dc.subject temporal lobe epilepsy model en
dc.subject translation initiation en
dc.title Phosphorylation of the ot subunit of translation initiation factor-2 by PKR mediates protein synthesis inhibition in the mouse brain during status epilepticus en
dc.type Artigo
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Indiana Univ
dc.description.affiliation Universidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, BR-04023062 São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Dept Fisiol, São Paulo, SP, Brazil
dc.description.affiliation Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, in USA
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Fisiol, São Paulo, SP, Brazil
dc.identifier.doi 10.1042/BJ20051643
dc.description.source Web of Science
dc.identifier.wos WOS:000238699200021



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