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Eukaryotic elongation factor 2 controls TNF-α translation in LPS-induced hepatitis.
González-Terán, Bárbara; Cortés, José R; Manieri, Elisa; Matesanz, Nuria; Verdugo, Ángeles; Rodríguez, María E; González-Rodríguez, Águeda; Valverde, Ángela M; Valverde, Ángela; Martín, Pilar; Davis, Roger J; Sabio, Guadalupe.
Afiliação
  • González-Terán B; Department of Vascular Biology and Inflammation, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
J Clin Invest ; 123(1): 164-78, 2013 Jan.
Article em En | MEDLINE | ID: mdl-23202732
Bacterial LPS (endotoxin) has been implicated in the pathogenesis of acute liver disease through its induction of the proinflammatory cytokine TNF-α. TNF-α is a key determinant of the outcome in a well-established mouse model of acute liver failure during septic shock. One possible mechanism for regulating TNF-α expression is through the control of protein elongation during translation, which would allow rapid cell adaptation to physiological changes. However, the regulation of translational elongation is poorly understood. We found that expression of p38γ/δ MAPK proteins is required for the elongation of nascent TNF-α protein in macrophages. The MKK3/6-p38γ/δ pathway mediated an inhibitory phosphorylation of eukaryotic elongation factor 2 (eEF2) kinase, which in turn promoted eEF2 activation (dephosphorylation) and subsequent TNF-α elongation. These results identify a new signaling pathway that regulates TNF-α production in LPS-induced liver damage and suggest potential cell-specific therapeutic targets for liver diseases in which TNF-α production is involved.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Elongação Traducional da Cadeia Peptídica / Lipopolissacarídeos / Fator de Necrose Tumoral alfa / Fator 2 de Elongação de Peptídeos / Sistema de Sinalização das MAP Quinases / Doença Hepática Induzida por Substâncias e Drogas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: J Clin Invest Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Espanha

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Elongação Traducional da Cadeia Peptídica / Lipopolissacarídeos / Fator de Necrose Tumoral alfa / Fator 2 de Elongação de Peptídeos / Sistema de Sinalização das MAP Quinases / Doença Hepática Induzida por Substâncias e Drogas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: J Clin Invest Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Espanha