Protection against gamma-radiation injury by protein tyrosine phosphatase 1B

Protein tyrosine phosphatase 1B (PTP1B) is widely expressed in mammalian tissues, in particular in immune cells, and plays a pleiotropic role in dephosphorylating many substrates. Moreover, PTP1B expression is enhanced in response to pro-inflammatory stimuli and to different cell stressors. Taking a...

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Autores: Mojena, Marina, Pimentel-Santillana, María, Povo-Retana, Adrián, Fernández-García, Victoria, González-Ramos, Silvia, Rada, Patricia, Tejedor, Alberto, Rico, Daniel, Martín-Sanz, Paloma, Valverde, Ángela M., Boscá, Lisardo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/177497
Acceso en línea:http://hdl.handle.net/10261/177497
Access Level:acceso abierto
Palabra clave:Cell viability
Irradiation sensitivity
Protein tyrosine phosphatase
Lethality
p53
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spelling Protection against gamma-radiation injury by protein tyrosine phosphatase 1BMojena, MarinaPimentel-Santillana, MaríaPovo-Retana, AdriánFernández-García, VictoriaGonzález-Ramos, SilviaRada, PatriciaTejedor, AlbertoRico, DanielMartín-Sanz, PalomaValverde, Ángela M.Boscá, LisardoCell viabilityIrradiation sensitivityProtein tyrosine phosphataseLethalityp53Protein tyrosine phosphatase 1B (PTP1B) is widely expressed in mammalian tissues, in particular in immune cells, and plays a pleiotropic role in dephosphorylating many substrates. Moreover, PTP1B expression is enhanced in response to pro-inflammatory stimuli and to different cell stressors. Taking advantage of the use of mice deficient in PTP1B we have investigated the effect of γ-radiation in these animals and found enhanced lethality and decreased respiratory exchange ratio vs. the corresponding wild type animals. Using bone-marrow derived macrophages and mouse embryonic fibroblasts (MEFs) from wild-type and PTP1B-deficient mice, we observed a differential response to various cell stressors. PTP1B-deficient macrophages exhibited an enhanced response to γ-radiation, UV-light, LPS and S-nitroso-glutathione. Macrophages exposed to γ-radiation show DNA damage and fragmentation, increased ROS production, a lack in GSH elevation and enhanced acidic β-galactosidase activity. Interestingly, these differences were not observed in MEFs. Differential gene expression analysis of WT and KO macrophages revealed that the main pathways affected after irradiation were an up-regulation of protein secretion, TGF-β signaling and angiogenesis among other, and downregulation of Myc targets and Hedgehog signaling. These results demonstrate a key role for PTP1B in the protection against the cytotoxicity of irradiation in intact animal and in macrophages, which might be therapeutically relevant.This work was supported by grants SAF2017-82436R, SAF2016-75004R and SAF2015-65267 from MINIECO, S2017/BMD-3686 and BMD3684 from Comunidad de Madrid, Fundación Ramón Areces (2016/CIVP18A3864) and Cibercv, Ciberdem and Ciberehd (funded by the Instituto de Salud Carlos III and by Fondos FEDER). We also acknowledge H2020 Marie Sklodowska-Curie ITN-TREATMENT (Grant Agreement number 721236) (European Commission). P.R. was recipient a Juan de la Cierva postdoctoral contract from MINIECO (IJCI-2014-19381).Peer ReviewedElsevierAgencia Estatal de Investigación (España)Ministerio de Economía y Competitividad (España)Fundación Ramón ArecesEuropean CommissionInstituto de Salud Carlos IIIMinisterio de Economía, Industria y Competitividad (España)Comunidad de MadridConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2019201920182019info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/177497reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#SAF2017-82436-R/AEI/10.13039/501100011033info:eu-repo/grantAgreement/EC/H2020/721236info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-75004-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/SAF2017-82436-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-65267-RS2017/BMD-3686/CIFRA2S2017/BMD-3684/MOIR2info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/IJCI-2014-19381https://doi.org/10.1016/j.redox.2018.04.018Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1774972026-05-22T06:33:51Z
dc.title.none.fl_str_mv Protection against gamma-radiation injury by protein tyrosine phosphatase 1B
title Protection against gamma-radiation injury by protein tyrosine phosphatase 1B
spellingShingle Protection against gamma-radiation injury by protein tyrosine phosphatase 1B
Mojena, Marina
Cell viability
Irradiation sensitivity
Protein tyrosine phosphatase
Lethality
p53
title_short Protection against gamma-radiation injury by protein tyrosine phosphatase 1B
title_full Protection against gamma-radiation injury by protein tyrosine phosphatase 1B
title_fullStr Protection against gamma-radiation injury by protein tyrosine phosphatase 1B
title_full_unstemmed Protection against gamma-radiation injury by protein tyrosine phosphatase 1B
title_sort Protection against gamma-radiation injury by protein tyrosine phosphatase 1B
dc.creator.none.fl_str_mv Mojena, Marina
Pimentel-Santillana, María
Povo-Retana, Adrián
Fernández-García, Victoria
González-Ramos, Silvia
Rada, Patricia
Tejedor, Alberto
Rico, Daniel
Martín-Sanz, Paloma
Valverde, Ángela M.
Boscá, Lisardo
author Mojena, Marina
author_facet Mojena, Marina
Pimentel-Santillana, María
Povo-Retana, Adrián
Fernández-García, Victoria
González-Ramos, Silvia
Rada, Patricia
Tejedor, Alberto
Rico, Daniel
Martín-Sanz, Paloma
Valverde, Ángela M.
Boscá, Lisardo
author_role author
author2 Pimentel-Santillana, María
Povo-Retana, Adrián
Fernández-García, Victoria
González-Ramos, Silvia
Rada, Patricia
Tejedor, Alberto
Rico, Daniel
Martín-Sanz, Paloma
Valverde, Ángela M.
Boscá, Lisardo
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Agencia Estatal de Investigación (España)
Ministerio de Economía y Competitividad (España)
Fundación Ramón Areces
European Commission
Instituto de Salud Carlos III
Ministerio de Economía, Industria y Competitividad (España)
Comunidad de Madrid
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Cell viability
Irradiation sensitivity
Protein tyrosine phosphatase
Lethality
p53
topic Cell viability
Irradiation sensitivity
Protein tyrosine phosphatase
Lethality
p53
description Protein tyrosine phosphatase 1B (PTP1B) is widely expressed in mammalian tissues, in particular in immune cells, and plays a pleiotropic role in dephosphorylating many substrates. Moreover, PTP1B expression is enhanced in response to pro-inflammatory stimuli and to different cell stressors. Taking advantage of the use of mice deficient in PTP1B we have investigated the effect of γ-radiation in these animals and found enhanced lethality and decreased respiratory exchange ratio vs. the corresponding wild type animals. Using bone-marrow derived macrophages and mouse embryonic fibroblasts (MEFs) from wild-type and PTP1B-deficient mice, we observed a differential response to various cell stressors. PTP1B-deficient macrophages exhibited an enhanced response to γ-radiation, UV-light, LPS and S-nitroso-glutathione. Macrophages exposed to γ-radiation show DNA damage and fragmentation, increased ROS production, a lack in GSH elevation and enhanced acidic β-galactosidase activity. Interestingly, these differences were not observed in MEFs. Differential gene expression analysis of WT and KO macrophages revealed that the main pathways affected after irradiation were an up-regulation of protein secretion, TGF-β signaling and angiogenesis among other, and downregulation of Myc targets and Hedgehog signaling. These results demonstrate a key role for PTP1B in the protection against the cytotoxicity of irradiation in intact animal and in macrophages, which might be therapeutically relevant.
publishDate 2018
dc.date.none.fl_str_mv 2018
2019
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/177497
url http://hdl.handle.net/10261/177497
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
SAF2017-82436-R/AEI/10.13039/501100011033
info:eu-repo/grantAgreement/EC/H2020/721236
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-75004-R
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/SAF2017-82436-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-65267-R
S2017/BMD-3686/CIFRA2
S2017/BMD-3684/MOIR2
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/IJCI-2014-19381
https://doi.org/10.1016/j.redox.2018.04.018
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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