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Chronically stressed or stress-preconditioned neurons fail to maintain stress granule assembly.
Shelkovnikova, Tatyana A; Dimasi, Pasquale; Kukharsky, Michail S; An, Haiyan; Quintiero, Annamaria; Schirmer, Claire; Buée, Luc; Galas, Marie-Christine; Buchman, Vladimir L.
Afiliação
  • Shelkovnikova TA; School of Biosciences, Cardiff University, Cardiff, UK.
  • Dimasi P; School of Biosciences, Cardiff University, Cardiff, UK.
  • Kukharsky MS; School of Biosciences, Cardiff University, Cardiff, UK.
  • An H; Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, Moscow Region, Russian Federation.
  • Quintiero A; School of Biosciences, Cardiff University, Cardiff, UK.
  • Schirmer C; School of Biosciences, Cardiff University, Cardiff, UK.
  • Buée L; University Lille, Inserm, CHU-Lille, UMRS1172, Alzheimer & Tauopathies, Lille, France.
  • Galas MC; University Lille, Inserm, CHU-Lille, UMRS1172, Alzheimer & Tauopathies, Lille, France.
  • Buchman VL; University Lille, Inserm, CHU-Lille, UMRS1172, Alzheimer & Tauopathies, Lille, France.
Cell Death Dis ; 8(5): e2788, 2017 05 11.
Article em En | MEDLINE | ID: mdl-28492545
ABSTRACT
Dysregulation of stress granules (SGs) and their resident proteins contributes to pathogenesis of a number of (neuro)degenerative diseases. Phosphorylation of eIF2α is an event integrating different types of cellular stress and it is required for SG assembly. Phosphorylated eIF2α (p-eIF2α) is upregulated in the nervous system in some neurodegenerative conditions. We found that increasing p-eIF2α level by proteasomal inhibition in cultured cells, including mouse and human neurons, before a SG-inducing stress ('stress preconditioning'), limits their ability to maintain SG assembly. This is due to upregulation of PP1 phosphatase regulatory subunits GADD34 and/or CReP in preconditioned cells and early decline of p-eIF2α levels during subsequent acute stress. In two model systems with constitutively upregulated p-eIF2α, mouse embryonic fibroblasts lacking CReP and brain neurons of tau transgenic mice, SG formation was also impaired. Thus, neurons enduring chronic stress or primed by a transient mild stress fail to maintain p-eIF2α levels following subsequent acute stress, which would compromise protective function of SGs. Our findings provide experimental evidence on possible loss of function for SGs in certain neurodegenerative diseases.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Estresse Fisiológico / Grânulos Citoplasmáticos / Proteínas do Tecido Nervoso / Neurônios Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Death Dis Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Estresse Fisiológico / Grânulos Citoplasmáticos / Proteínas do Tecido Nervoso / Neurônios Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Death Dis Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Reino Unido