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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

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....

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Autores principales: Badiola, N, Penas, C, Miñano-Molina, A, Barneda-Zahonero, B, Fadó, R, Sánchez-Opazo, G, Comella, J X, Sabriá, J, Zhu, C, Blomgren, K, Casas, C, Rodríguez-Alvarez, J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122062/
https://www.ncbi.nlm.nih.gov/pubmed/21525936
http://dx.doi.org/10.1038/cddis.2011.31
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author Badiola, N
Penas, C
Miñano-Molina, A
Barneda-Zahonero, B
Fadó, R
Sánchez-Opazo, G
Comella, J X
Sabriá, J
Zhu, C
Blomgren, K
Casas, C
Rodríguez-Alvarez, J
author_facet Badiola, N
Penas, C
Miñano-Molina, A
Barneda-Zahonero, B
Fadó, R
Sánchez-Opazo, G
Comella, J X
Sabriá, J
Zhu, C
Blomgren, K
Casas, C
Rodríguez-Alvarez, J
author_sort Badiola, N
collection PubMed
description 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.
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spelling pubmed-31220622011-07-05 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, N Penas, C Miñano-Molina, A Barneda-Zahonero, B Fadó, R Sánchez-Opazo, G Comella, J X Sabriá, J Zhu, C Blomgren, K Casas, C Rodríguez-Alvarez, J Cell Death Dis Original Article 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. Nature Publishing Group 2011-04 2011-04-28 /pmc/articles/PMC3122062/ /pubmed/21525936 http://dx.doi.org/10.1038/cddis.2011.31 Text en Copyright © 2011 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ 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/
spellingShingle Original Article
Badiola, N
Penas, C
Miñano-Molina, A
Barneda-Zahonero, B
Fadó, R
Sánchez-Opazo, G
Comella, J X
Sabriá, J
Zhu, C
Blomgren, K
Casas, C
Rodríguez-Alvarez, J
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122062/
https://www.ncbi.nlm.nih.gov/pubmed/21525936
http://dx.doi.org/10.1038/cddis.2011.31
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