Induction of ER stress in response to oxygen-glucose deprivation of cortical cultures involves the activation of the PERK and IRE-1 pathways and of caspase-12
Badiola Benito, Nahuai (Universitat Autònoma de Barcelona. Institut de Neurociències)
Penas Pérez, Clara (Universitat Autònoma de Barcelona. Institut de Neurociències)
Miñano Molina, Alfredo Jesús (Universitat Autònoma de Barcelona. Institut de Neurociències)
Barneda Zahonero, Bruna (Universitat Autònoma de Barcelona. Institut de Neurociències)
Fadó, Rut (Universitat Autònoma de Barcelona. Institut de Neurociències)
Sánchez Opazo, Guillem (Universitat Autònoma de Barcelona. Institut de Neurociències)
Comella i Carnicé, Joan Xavier, 1963- (Universitat Autònoma de Barcelona. Institut de Neurociències)
Sabrià i Pau, Josefa (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Zhu, Chao (University of Gothenburg. Institute of Neuroscience and Physiology)
Blomgren, K. (University of Gothenburg. Institute of Neuroscience and Physiology)
Casas Louzao, Caty (Universitat Autònoma de Barcelona. Institut de Neurociències)
Rodríguez Álvarez, José (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Date:	2011
Abstract:	Disturbance of calcium homeostasis and accumulation of misfolded proteins in the endoplasmic reticulum (ER) are considered contributory components of cell death after ischemia. However, the signal-transducing events that are activated by ER stress after cerebral ischemia are incompletely understood. In this study, we show that caspase-12 and the PERK and IRE pathways are activated following oxygen-glucose deprivation (OGD) of mixed cortical cultures or neonatal hypoxia-ischemia (HI). Activation of PERK led to a transient phosphorylation of eIF2α, an increase in ATF4 levels and the induction of gadd34 (a subunit of an eIF2α-directed phosphatase). Interestingly, the upregulation of ATF4 did not lead to an increase in the levels of CHOP. Additionally, IRE1 activation was mediated by the increase in the processed form of xbp1, which would be responsible for the observed expression of edem2 and the increased levels of the chaperones GRP78 and GRP94. We were also able to detect caspase-12 proteolysis after HI or OGD. Processing of procaspase-12 was mediated by NMDA receptor and calpain activation. Moreover, our data suggest that caspase-12 activation is independent of the unfolded protein response activated by ER stress.
Grants:	Ministerio de Ciencia y Tecnología SAF2005-05106 Ministerio de Ciencia y Tecnología SAF2008-01904
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Endoplasmic reticulum stress ; Apoptosis ; Caspase-12 ; Ischemia ; Cell culture ; Brain
Published in:	Cell death and disease, Vol. 2 (April 2011) , art. e149, ISSN 2041-4889

DOI: 10.1038/cddis.2011.31
PMID: 21525936

8 p, 491.4 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles