Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes

BACKGROUND: cAMP signaling produces dramatic changes in astrocyte morphology and physiology. However, its involvement in phenotype acquisition and the transcriptionally mediated mechanisms of action are largely unknown. RESULTS: Here we analyzed the global transcriptome of cultured astroglial cells...

Descripción completa

Detalles Bibliográficos
Autores: Paco, Sonia, Hummel, Manuela, Plá, Virginia, Sumoy Van Dyck, Lauro, Aguado, Fernando
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/26795
Acceso en línea:http://hdl.handle.net/10230/26795
http://dx.doi.org/10.1186/s12864-016-2623-4
Access Level:acceso abierto
Palabra clave:Antioxidants
Antioxidant defense
Astrocytes
Brain
Differentiation
NR2C
Reactive glia
Transcriptomic
cAMP
id ES_9276b045682149d321dff4852c0ec3d2
oai_identifier_str oai:repositori.upf.edu:10230/26795
network_acronym_str ES
network_name_str España
repository_id_str
spelling Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytesPaco, SoniaHummel, ManuelaPlá, VirginiaSumoy Van Dyck, LauroAguado, FernandoAntioxidantsAntioxidant defenseAstrocytesBrainDifferentiationNR2CReactive gliaTranscriptomiccAMPBACKGROUND: cAMP signaling produces dramatic changes in astrocyte morphology and physiology. However, its involvement in phenotype acquisition and the transcriptionally mediated mechanisms of action are largely unknown. RESULTS: Here we analyzed the global transcriptome of cultured astroglial cells incubated with activators of cAMP pathways. A bulk of astroglial transcripts, 6221 annotated genes, were differentially regulated by cAMP signaling. cAMP analogs strongly upregulated genes involved in typical functions of mature astrocytes, such as homeostatic control, metabolic and structural support to neurons, antioxidant defense and communication, whereas they downregulated a considerable number of proliferating and immaturity-related transcripts. Moreover, numerous genes typically activated in reactive cells, such as scar components and immunological mediators, were repressed by cAMP. GSEA analysis contrasting gene expression profiles with transcriptome signatures of acutely isolated astrocytes and in situ evaluation of protein levels in these cells showed that cAMP signaling conferred mature and in vivo-like transcriptional features to cultured astrocytes. CONCLUSIONS: These results indicate that cAMP signaling is a key pathway promoting astrocyte maturation and restricting their developmental and activation features. Therefore, a positive modulation of cAMP signaling may promote the normal state of differentiated astrocytes and favor the protection and function of neuronal networks.This work was supported by grants from Spanish Ministry of Economy and Competitiveness (BFU2010-22132 and BFU2013-48822-R) and from Catalonian Government (2014SGR-01178) to F.ABioMed Central201620162016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/26795http://dx.doi.org/10.1186/s12864-016-2623-4reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésBMC Genomics. 2016; 17(1): 304© 2016 Paco et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/267952026-06-12T07:21:37Z
dc.title.none.fl_str_mv Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes
title Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes
spellingShingle Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes
Paco, Sonia
Antioxidants
Antioxidant defense
Astrocytes
Brain
Differentiation
NR2C
Reactive glia
Transcriptomic
cAMP
title_short Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes
title_full Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes
title_fullStr Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes
title_full_unstemmed Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes
title_sort Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes
dc.creator.none.fl_str_mv Paco, Sonia
Hummel, Manuela
Plá, Virginia
Sumoy Van Dyck, Lauro
Aguado, Fernando
author Paco, Sonia
author_facet Paco, Sonia
Hummel, Manuela
Plá, Virginia
Sumoy Van Dyck, Lauro
Aguado, Fernando
author_role author
author2 Hummel, Manuela
Plá, Virginia
Sumoy Van Dyck, Lauro
Aguado, Fernando
author2_role author
author
author
author
dc.subject.none.fl_str_mv Antioxidants
Antioxidant defense
Astrocytes
Brain
Differentiation
NR2C
Reactive glia
Transcriptomic
cAMP
topic Antioxidants
Antioxidant defense
Astrocytes
Brain
Differentiation
NR2C
Reactive glia
Transcriptomic
cAMP
description BACKGROUND: cAMP signaling produces dramatic changes in astrocyte morphology and physiology. However, its involvement in phenotype acquisition and the transcriptionally mediated mechanisms of action are largely unknown. RESULTS: Here we analyzed the global transcriptome of cultured astroglial cells incubated with activators of cAMP pathways. A bulk of astroglial transcripts, 6221 annotated genes, were differentially regulated by cAMP signaling. cAMP analogs strongly upregulated genes involved in typical functions of mature astrocytes, such as homeostatic control, metabolic and structural support to neurons, antioxidant defense and communication, whereas they downregulated a considerable number of proliferating and immaturity-related transcripts. Moreover, numerous genes typically activated in reactive cells, such as scar components and immunological mediators, were repressed by cAMP. GSEA analysis contrasting gene expression profiles with transcriptome signatures of acutely isolated astrocytes and in situ evaluation of protein levels in these cells showed that cAMP signaling conferred mature and in vivo-like transcriptional features to cultured astrocytes. CONCLUSIONS: These results indicate that cAMP signaling is a key pathway promoting astrocyte maturation and restricting their developmental and activation features. Therefore, a positive modulation of cAMP signaling may promote the normal state of differentiated astrocytes and favor the protection and function of neuronal networks.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/26795
http://dx.doi.org/10.1186/s12864-016-2623-4
url http://hdl.handle.net/10230/26795
http://dx.doi.org/10.1186/s12864-016-2623-4
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv BMC Genomics. 2016; 17(1): 304
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869413473016872960
score 15,811543

Similares en LA Referencia