Calcineurin β protects brain after injury by activating the unfolded protein response

Autores
Chen, Yanan; Holstein, Deborah M.; Aime, Sofía; Bollo, Mariana Ines; Lechleiter, James D.
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The Ca2 +-dependent phosphatase, calcineurin (CN) is thought to play a detrimental role in damaged neurons; however, its role in astrocytes is unclear. In cultured astrocytes, CNβ expression increased after treatment with a sarco/endoplasmic reticulum Ca2 +-ATPase inhibitor, thapsigargin, and with oxygen and glucose deprivation, an in vitro model of ischemia. Similarly, CNβ was induced in astrocytes in vivo in two different mouse models of brain injury - photothrombotic stroke and traumatic brain injury (TBI). Immunoprecipitation and chemical activation dimerization methods pointed to physical interaction of CNβ with the unfolded protein response (UPR) sensor, protein kinase RNA-like endoplasmic reticulum kinase (PERK). In accordance, induction of CNβ resulted in oligomerization and activation of PERK. Strikingly, the presence of a phosphatase inhibitor did not interfere with CNβ-mediated activation of PERK, suggesting a hitherto undiscovered non-enzymatic role for CNβ. Importantly, the cytoprotective function of CNβ was PERK-dependent both in vitro and in vivo. Loss of CNβ in vivo resulted in a significant increase in cerebral damage, and correlated with a decrease in astrocyte size, PERK activity and glial fibrillary acidic protein (GFAP) expression. Taken together, these data reveal a critical role for the CNβ-PERK axis in not only prolonging astrocyte cell survival but also in modulating astrogliosis after brain injury.
Fil: Chen, Yanan. University of Texas Health Science Center at San Antonio; Estados Unidos
Fil: Holstein, Deborah M.. University of Texas Health Science Center at San Antonio; Estados Unidos
Fil: Aime, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Bollo, Mariana Ines. University of Texas Health Science Center at San Antonio; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Lechleiter, James D.. University of Texas Health Science Center at San Antonio; Estados Unidos
Materia
CALCIUM
ENDOPLASMIC RETICULUM
ISCHEMIA
STRESS
TRAUMATIC BRAIN INJURY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/76716
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/76716
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Calcineurin β protects brain after injury by activating the unfolded protein responseChen, YananHolstein, Deborah M.Aime, SofíaBollo, Mariana InesLechleiter, James D.CALCIUMENDOPLASMIC RETICULUMISCHEMIASTRESSTRAUMATIC BRAIN INJURYhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The Ca2 +-dependent phosphatase, calcineurin (CN) is thought to play a detrimental role in damaged neurons; however, its role in astrocytes is unclear. In cultured astrocytes, CNβ expression increased after treatment with a sarco/endoplasmic reticulum Ca2 +-ATPase inhibitor, thapsigargin, and with oxygen and glucose deprivation, an in vitro model of ischemia. Similarly, CNβ was induced in astrocytes in vivo in two different mouse models of brain injury - photothrombotic stroke and traumatic brain injury (TBI). Immunoprecipitation and chemical activation dimerization methods pointed to physical interaction of CNβ with the unfolded protein response (UPR) sensor, protein kinase RNA-like endoplasmic reticulum kinase (PERK). In accordance, induction of CNβ resulted in oligomerization and activation of PERK. Strikingly, the presence of a phosphatase inhibitor did not interfere with CNβ-mediated activation of PERK, suggesting a hitherto undiscovered non-enzymatic role for CNβ. Importantly, the cytoprotective function of CNβ was PERK-dependent both in vitro and in vivo. Loss of CNβ in vivo resulted in a significant increase in cerebral damage, and correlated with a decrease in astrocyte size, PERK activity and glial fibrillary acidic protein (GFAP) expression. Taken together, these data reveal a critical role for the CNβ-PERK axis in not only prolonging astrocyte cell survival but also in modulating astrogliosis after brain injury.Fil: Chen, Yanan. University of Texas Health Science Center at San Antonio; Estados UnidosFil: Holstein, Deborah M.. University of Texas Health Science Center at San Antonio; Estados UnidosFil: Aime, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Bollo, Mariana Ines. University of Texas Health Science Center at San Antonio; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Lechleiter, James D.. University of Texas Health Science Center at San Antonio; Estados UnidosAcademic Press Inc Elsevier Science2016-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/76716Chen, Yanan; Holstein, Deborah M.; Aime, Sofía; Bollo, Mariana Ines; Lechleiter, James D.; Calcineurin β protects brain after injury by activating the unfolded protein response; Academic Press Inc Elsevier Science; Neurobiology of Disease; 94; 10-2016; 139-1560969-9961CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0969996116301449info:eu-repo/semantics/altIdentifier/doi/10.1016/j.nbd.2016.06.011info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:09:06Zoai:ri.conicet.gov.ar:11336/76716instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:09:06.571CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Calcineurin β protects brain after injury by activating the unfolded protein response
title Calcineurin β protects brain after injury by activating the unfolded protein response
spellingShingle Calcineurin β protects brain after injury by activating the unfolded protein response
Chen, Yanan
CALCIUM
ENDOPLASMIC RETICULUM
ISCHEMIA
STRESS
TRAUMATIC BRAIN INJURY
title_short Calcineurin β protects brain after injury by activating the unfolded protein response
title_full Calcineurin β protects brain after injury by activating the unfolded protein response
title_fullStr Calcineurin β protects brain after injury by activating the unfolded protein response
title_full_unstemmed Calcineurin β protects brain after injury by activating the unfolded protein response
title_sort Calcineurin β protects brain after injury by activating the unfolded protein response
dc.creator.none.fl_str_mv Chen, Yanan
Holstein, Deborah M.
Aime, Sofía
Bollo, Mariana Ines
Lechleiter, James D.
author Chen, Yanan
author_facet Chen, Yanan
Holstein, Deborah M.
Aime, Sofía
Bollo, Mariana Ines
Lechleiter, James D.
author_role author
author2 Holstein, Deborah M.
Aime, Sofía
Bollo, Mariana Ines
Lechleiter, James D.
author2_role author
author
author
author
dc.subject.none.fl_str_mv CALCIUM
ENDOPLASMIC RETICULUM
ISCHEMIA
STRESS
TRAUMATIC BRAIN INJURY
topic CALCIUM
ENDOPLASMIC RETICULUM
ISCHEMIA
STRESS
TRAUMATIC BRAIN INJURY
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The Ca2 +-dependent phosphatase, calcineurin (CN) is thought to play a detrimental role in damaged neurons; however, its role in astrocytes is unclear. In cultured astrocytes, CNβ expression increased after treatment with a sarco/endoplasmic reticulum Ca2 +-ATPase inhibitor, thapsigargin, and with oxygen and glucose deprivation, an in vitro model of ischemia. Similarly, CNβ was induced in astrocytes in vivo in two different mouse models of brain injury - photothrombotic stroke and traumatic brain injury (TBI). Immunoprecipitation and chemical activation dimerization methods pointed to physical interaction of CNβ with the unfolded protein response (UPR) sensor, protein kinase RNA-like endoplasmic reticulum kinase (PERK). In accordance, induction of CNβ resulted in oligomerization and activation of PERK. Strikingly, the presence of a phosphatase inhibitor did not interfere with CNβ-mediated activation of PERK, suggesting a hitherto undiscovered non-enzymatic role for CNβ. Importantly, the cytoprotective function of CNβ was PERK-dependent both in vitro and in vivo. Loss of CNβ in vivo resulted in a significant increase in cerebral damage, and correlated with a decrease in astrocyte size, PERK activity and glial fibrillary acidic protein (GFAP) expression. Taken together, these data reveal a critical role for the CNβ-PERK axis in not only prolonging astrocyte cell survival but also in modulating astrogliosis after brain injury.
Fil: Chen, Yanan. University of Texas Health Science Center at San Antonio; Estados Unidos
Fil: Holstein, Deborah M.. University of Texas Health Science Center at San Antonio; Estados Unidos
Fil: Aime, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Bollo, Mariana Ines. University of Texas Health Science Center at San Antonio; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Lechleiter, James D.. University of Texas Health Science Center at San Antonio; Estados Unidos
description The Ca2 +-dependent phosphatase, calcineurin (CN) is thought to play a detrimental role in damaged neurons; however, its role in astrocytes is unclear. In cultured astrocytes, CNβ expression increased after treatment with a sarco/endoplasmic reticulum Ca2 +-ATPase inhibitor, thapsigargin, and with oxygen and glucose deprivation, an in vitro model of ischemia. Similarly, CNβ was induced in astrocytes in vivo in two different mouse models of brain injury - photothrombotic stroke and traumatic brain injury (TBI). Immunoprecipitation and chemical activation dimerization methods pointed to physical interaction of CNβ with the unfolded protein response (UPR) sensor, protein kinase RNA-like endoplasmic reticulum kinase (PERK). In accordance, induction of CNβ resulted in oligomerization and activation of PERK. Strikingly, the presence of a phosphatase inhibitor did not interfere with CNβ-mediated activation of PERK, suggesting a hitherto undiscovered non-enzymatic role for CNβ. Importantly, the cytoprotective function of CNβ was PERK-dependent both in vitro and in vivo. Loss of CNβ in vivo resulted in a significant increase in cerebral damage, and correlated with a decrease in astrocyte size, PERK activity and glial fibrillary acidic protein (GFAP) expression. Taken together, these data reveal a critical role for the CNβ-PERK axis in not only prolonging astrocyte cell survival but also in modulating astrogliosis after brain injury.
publishDate 2016
dc.date.none.fl_str_mv 2016-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/76716
Chen, Yanan; Holstein, Deborah M.; Aime, Sofía; Bollo, Mariana Ines; Lechleiter, James D.; Calcineurin β protects brain after injury by activating the unfolded protein response; Academic Press Inc Elsevier Science; Neurobiology of Disease; 94; 10-2016; 139-156
0969-9961
CONICET Digital
CONICET
url http://hdl.handle.net/11336/76716
identifier_str_mv Chen, Yanan; Holstein, Deborah M.; Aime, Sofía; Bollo, Mariana Ines; Lechleiter, James D.; Calcineurin β protects brain after injury by activating the unfolded protein response; Academic Press Inc Elsevier Science; Neurobiology of Disease; 94; 10-2016; 139-156
0969-9961
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0969996116301449
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.nbd.2016.06.011
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.993085

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