TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo

Autores
Belkacemi, Thabet; Niermann, Alexander; Hofmann, Laura; Wissenbach, Ulrich; Birnbaumer, Lutz; Leidinger, Petra; Backes, Christina; Meese, Eckart; Keller, Andreas; Bai, Xianshu; Scheller, Anja; Kirchhoff, Frank; Philipp, Stephan E.; Weissgerber, Petra; Flockerzi, Veit; Beck, Andreas
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión aceptada
Descripción
Fil: Belkacemi, Thabet. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania
Fil: Niermann, Alexander. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania
Fil: Hofmann, Laura. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania
Fil: Wissenbach, Ulrich. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania
Fil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Research Triangle Park. Neurobiology Laboratory; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Leidinger, Petra. Universität des Saarlandes. Institut für Humangenetik; Alemania
Fil: Backes, Christina. Universität des Saarlandes. Klinische Bioinformatik; Alemania
Fil: Meese, Eckart. Universität des Saarlandes. Institut für Humangenetik; Alemania
Fil: Keller, Andreas. Universität des Saarlandes. Klinische Bioinformatik; Alemania
Fil: Bai, Xianshu. Universität des Saarlandes. Molekulare Physiologie; Alemania
Fil: Scheller, Anja. Universität des Saarlandes. Molekulare Physiologie; Alemania
Fil: Kirchhoff, Frank. Universität des Saarlandes. Molekulare Physiologie; Alemania
Fil: Philipp, Stephan E. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania
Fil: Weissgerber, Petra. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania
Fil: Flockerzi, Veit. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania
Fil: Beck, Andreas. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania
Fil: Beck, Andreas. Universität des Saarlandes. Molekulare Physiologie; Alemania
Abstract: Following brain injury astrocytes change into a reactive state, proliferate and grow into the site of lesion, a process called astrogliosis, initiated and regulated by changes in cytoplasmic Ca2+ . Transient receptor potential canonical (TRPC) channels may contribute to Ca2+ influx but their presence and possible function in astrocytes is not known. By RT-PCR and RNA sequencing we identified transcripts of Trpc1, Trpc2, Trpc3, and Trpc4 in FACS-sorted glutamate aspartate transporter (GLAST)-positive cultured mouse cortical astrocytes and subcloned full-length Trpc1 and Trpc3 cDNAs from these cells. Ca2+ entry in cortical astrocytes depended on TRPC3 and was increased in the absence of Trpc1. After co-expression of Trpc1 and Trpc3 in HEK-293 cells both proteins co-immunoprecipitate and form functional heteromeric channels, with TRPC1 reducing TRPC3 activity. In vitro, lack of Trpc3 reduced astrocyte proliferation and migration whereas the TRPC3 gain-of-function moonwalker mutation and Trpc1 deficiency increased astrocyte migration. In vivo, astrogliosis and cortex edema following stab wound injury were reduced in Trpc3-/- but increased in Trpc1-/- mice. In summary, our results show a decisive contribution of TRPC3 to astrocyte Ca2+ signaling, which is even augmented in the absence of Trpc1, in particular following brain injury. Targeted therapies to reduce TRPC3 channel activity in astrocytes might therefore be beneficial in traumatic brain injury.
Fuente
Glia. 2017;65(9):1535-1549
Materia
TEJIDO NERVIOSO
CELULAS
CEREBRO
CORTEZA CEREBRAL
HERIDAS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
Repositorio Institucional (UCA)
Institución
Pontificia Universidad Católica Argentina
OAI Identificador
oai:ucacris:123456789/8724
Acceder
id RIUCA_d9ed92999c0504c52c808ab0cea7b023
oai_identifier_str oai:ucacris:123456789/8724
network_acronym_str RIUCA
repository_id_str 2585
network_name_str Repositorio Institucional (UCA)
spelling TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivoBelkacemi, ThabetNiermann, AlexanderHofmann, LauraWissenbach, UlrichBirnbaumer, LutzLeidinger, PetraBackes, ChristinaMeese, EckartKeller, AndreasBai, XianshuScheller, AnjaKirchhoff, FrankPhilipp, Stephan E.Weissgerber, PetraFlockerzi, VeitBeck, AndreasTEJIDO NERVIOSOCELULASCEREBROCORTEZA CEREBRALHERIDASFil: Belkacemi, Thabet. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; AlemaniaFil: Niermann, Alexander. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; AlemaniaFil: Hofmann, Laura. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; AlemaniaFil: Wissenbach, Ulrich. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; AlemaniaFil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Research Triangle Park. Neurobiology Laboratory; Estados UnidosFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; ArgentinaFil: Leidinger, Petra. Universität des Saarlandes. Institut für Humangenetik; AlemaniaFil: Backes, Christina. Universität des Saarlandes. Klinische Bioinformatik; AlemaniaFil: Meese, Eckart. Universität des Saarlandes. Institut für Humangenetik; AlemaniaFil: Keller, Andreas. Universität des Saarlandes. Klinische Bioinformatik; AlemaniaFil: Bai, Xianshu. Universität des Saarlandes. Molekulare Physiologie; AlemaniaFil: Scheller, Anja. Universität des Saarlandes. Molekulare Physiologie; AlemaniaFil: Kirchhoff, Frank. Universität des Saarlandes. Molekulare Physiologie; AlemaniaFil: Philipp, Stephan E. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; AlemaniaFil: Weissgerber, Petra. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; AlemaniaFil: Flockerzi, Veit. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; AlemaniaFil: Beck, Andreas. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; AlemaniaFil: Beck, Andreas. Universität des Saarlandes. Molekulare Physiologie; AlemaniaAbstract: Following brain injury astrocytes change into a reactive state, proliferate and grow into the site of lesion, a process called astrogliosis, initiated and regulated by changes in cytoplasmic Ca2+ . Transient receptor potential canonical (TRPC) channels may contribute to Ca2+ influx but their presence and possible function in astrocytes is not known. By RT-PCR and RNA sequencing we identified transcripts of Trpc1, Trpc2, Trpc3, and Trpc4 in FACS-sorted glutamate aspartate transporter (GLAST)-positive cultured mouse cortical astrocytes and subcloned full-length Trpc1 and Trpc3 cDNAs from these cells. Ca2+ entry in cortical astrocytes depended on TRPC3 and was increased in the absence of Trpc1. After co-expression of Trpc1 and Trpc3 in HEK-293 cells both proteins co-immunoprecipitate and form functional heteromeric channels, with TRPC1 reducing TRPC3 activity. In vitro, lack of Trpc3 reduced astrocyte proliferation and migration whereas the TRPC3 gain-of-function moonwalker mutation and Trpc1 deficiency increased astrocyte migration. In vivo, astrogliosis and cortex edema following stab wound injury were reduced in Trpc3-/- but increased in Trpc1-/- mice. In summary, our results show a decisive contribution of TRPC3 to astrocyte Ca2+ signaling, which is even augmented in the absence of Trpc1, in particular following brain injury. Targeted therapies to reduce TRPC3 channel activity in astrocytes might therefore be beneficial in traumatic brain injury.Wiley2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://repositorio.uca.edu.ar/handle/123456789/87241098-113610.1002/glia.2318028636132Belkacemi T, Niermann A, Hofmann L, et al. TRPC1‐ and TRPC3‐dependent Ca2+ signaling in mouse cortical astrocytes affects injury‐evoked astrogliosis in vivo [en línea]. Glia. 2017;65(9):1535-1549. doi:10.1002/glia.23180 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8724Glia. 2017;65(9):1535-1549reponame:Repositorio Institucional (UCA)instname:Pontificia Universidad Católica Argentinaenginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/4.0/2025-07-03T10:56:54Zoai:ucacris:123456789/8724instacron:UCAInstitucionalhttps://repositorio.uca.edu.ar/Universidad privadaNo correspondehttps://repositorio.uca.edu.ar/oaiclaudia_fernandez@uca.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:25852025-07-03 10:56:55.12Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentinafalse
dc.title.none.fl_str_mv TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
title TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
spellingShingle TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
Belkacemi, Thabet
TEJIDO NERVIOSO
CELULAS
CEREBRO
CORTEZA CEREBRAL
HERIDAS
title_short TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
title_full TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
title_fullStr TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
title_full_unstemmed TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
title_sort TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
dc.creator.none.fl_str_mv Belkacemi, Thabet
Niermann, Alexander
Hofmann, Laura
Wissenbach, Ulrich
Birnbaumer, Lutz
Leidinger, Petra
Backes, Christina
Meese, Eckart
Keller, Andreas
Bai, Xianshu
Scheller, Anja
Kirchhoff, Frank
Philipp, Stephan E.
Weissgerber, Petra
Flockerzi, Veit
Beck, Andreas
author Belkacemi, Thabet
author_facet Belkacemi, Thabet
Niermann, Alexander
Hofmann, Laura
Wissenbach, Ulrich
Birnbaumer, Lutz
Leidinger, Petra
Backes, Christina
Meese, Eckart
Keller, Andreas
Bai, Xianshu
Scheller, Anja
Kirchhoff, Frank
Philipp, Stephan E.
Weissgerber, Petra
Flockerzi, Veit
Beck, Andreas
author_role author
author2 Niermann, Alexander
Hofmann, Laura
Wissenbach, Ulrich
Birnbaumer, Lutz
Leidinger, Petra
Backes, Christina
Meese, Eckart
Keller, Andreas
Bai, Xianshu
Scheller, Anja
Kirchhoff, Frank
Philipp, Stephan E.
Weissgerber, Petra
Flockerzi, Veit
Beck, Andreas
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv TEJIDO NERVIOSO
CELULAS
CEREBRO
CORTEZA CEREBRAL
HERIDAS
topic TEJIDO NERVIOSO
CELULAS
CEREBRO
CORTEZA CEREBRAL
HERIDAS
dc.description.none.fl_txt_mv Fil: Belkacemi, Thabet. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania
Fil: Niermann, Alexander. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania
Fil: Hofmann, Laura. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania
Fil: Wissenbach, Ulrich. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania
Fil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Research Triangle Park. Neurobiology Laboratory; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Leidinger, Petra. Universität des Saarlandes. Institut für Humangenetik; Alemania
Fil: Backes, Christina. Universität des Saarlandes. Klinische Bioinformatik; Alemania
Fil: Meese, Eckart. Universität des Saarlandes. Institut für Humangenetik; Alemania
Fil: Keller, Andreas. Universität des Saarlandes. Klinische Bioinformatik; Alemania
Fil: Bai, Xianshu. Universität des Saarlandes. Molekulare Physiologie; Alemania
Fil: Scheller, Anja. Universität des Saarlandes. Molekulare Physiologie; Alemania
Fil: Kirchhoff, Frank. Universität des Saarlandes. Molekulare Physiologie; Alemania
Fil: Philipp, Stephan E. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania
Fil: Weissgerber, Petra. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania
Fil: Flockerzi, Veit. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania
Fil: Beck, Andreas. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania
Fil: Beck, Andreas. Universität des Saarlandes. Molekulare Physiologie; Alemania
Abstract: Following brain injury astrocytes change into a reactive state, proliferate and grow into the site of lesion, a process called astrogliosis, initiated and regulated by changes in cytoplasmic Ca2+ . Transient receptor potential canonical (TRPC) channels may contribute to Ca2+ influx but their presence and possible function in astrocytes is not known. By RT-PCR and RNA sequencing we identified transcripts of Trpc1, Trpc2, Trpc3, and Trpc4 in FACS-sorted glutamate aspartate transporter (GLAST)-positive cultured mouse cortical astrocytes and subcloned full-length Trpc1 and Trpc3 cDNAs from these cells. Ca2+ entry in cortical astrocytes depended on TRPC3 and was increased in the absence of Trpc1. After co-expression of Trpc1 and Trpc3 in HEK-293 cells both proteins co-immunoprecipitate and form functional heteromeric channels, with TRPC1 reducing TRPC3 activity. In vitro, lack of Trpc3 reduced astrocyte proliferation and migration whereas the TRPC3 gain-of-function moonwalker mutation and Trpc1 deficiency increased astrocyte migration. In vivo, astrogliosis and cortex edema following stab wound injury were reduced in Trpc3-/- but increased in Trpc1-/- mice. In summary, our results show a decisive contribution of TRPC3 to astrocyte Ca2+ signaling, which is even augmented in the absence of Trpc1, in particular following brain injury. Targeted therapies to reduce TRPC3 channel activity in astrocytes might therefore be beneficial in traumatic brain injury.
description Fil: Belkacemi, Thabet. Universität des Saarlandes. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://repositorio.uca.edu.ar/handle/123456789/8724
1098-1136
10.1002/glia.23180
28636132
Belkacemi T, Niermann A, Hofmann L, et al. TRPC1‐ and TRPC3‐dependent Ca2+ signaling in mouse cortical astrocytes affects injury‐evoked astrogliosis in vivo [en línea]. Glia. 2017;65(9):1535-1549. doi:10.1002/glia.23180 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8724
url https://repositorio.uca.edu.ar/handle/123456789/8724
identifier_str_mv 1098-1136
10.1002/glia.23180
28636132
Belkacemi T, Niermann A, Hofmann L, et al. TRPC1‐ and TRPC3‐dependent Ca2+ signaling in mouse cortical astrocytes affects injury‐evoked astrogliosis in vivo [en línea]. Glia. 2017;65(9):1535-1549. doi:10.1002/glia.23180 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8724
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/4.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv Glia. 2017;65(9):1535-1549
reponame:Repositorio Institucional (UCA)
instname:Pontificia Universidad Católica Argentina
reponame_str Repositorio Institucional (UCA)
collection Repositorio Institucional (UCA)
instname_str Pontificia Universidad Católica Argentina
repository.name.fl_str_mv Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentina
repository.mail.fl_str_mv claudia_fernandez@uca.edu.ar
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score 13.069144

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