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
Author
Badiola, Nahuai
Penas, Clara
Miñano Molina, Alfredo Jesús
Barneda-Zahonero, Bruna
Fadó Andrés, Rut
Sánchez-Opazo, G.
Comella, Joan X.
Sabrià, Josefa
Zhu, Chuanshuai
Blomgren, Klas
Casas, Caty
Rodríguez-Álvarez, José
Publication date
2011-04-28ISSN
2041-4889
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 eIF2a, an increase in ATF4 levels and the induction of gadd34 (a subunit of an eIF2adirected 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.
Document Type
Article
Document version
Accepted version
Language
English
Keywords
Cervell
Isquèmia
Apoptosi
Reticle endoplasmàtic
Cultius cel·lulars
Neurones
Sistema nerviós -- Degeneració
Cerebro
Isquemia
Apoptosis
Neuronas
Sistema nervioso -- Degeneración
Endoplasmic Reticulum Stress
Apoptosis
Ischemia
Cell culture
Brain
Nervous system
Pages
8
Publisher
Springer Nature
Collection
2;149
Is part of
Cell Death and Disease
Citation
Badiola, Nahuai; Penas, Clara; Miñano-Molina, Alfredo; Barneda-Zahonero, Bruna; Fadó, R.; Sánchez-Opazo, G.; Comella, Joan X.; Sabrià, Josefa; Zhu, Chuanshuai; Blomgren, Klas; Casas, Caty; Rodríguez-Alvarez, José. 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. Cell Death and Disease, 2011, vol. 2, núm. 149, p. 1-8. Disponible en: <https://www.nature.com/articles/cddis201131>. Fecha de acceso: 23 nov. 2019. DOI: 10.1038/cddis.2011.31.
Grant agreement number
eu-repo/grantAgreement/ES/3PN/SAF2008-01904
eu-repo/grantAgreement/ES/2PN/SAF2005-05106
This item appears in the following Collection(s)
- Ciències de la Salut [725]
Rights
Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under the Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-nd/3.0/