Deficit of mitogen-activated protein kinase phosphatase 1 (Dusp1) accelerates progressive hearing loss

Mitogen-activated protein kinases (MAPK) such as p38 and the c-Jun N-terminal kinases (JNKs) are activated during the cellular response to stress signals. Their activity is regulated by the MAPK-phosphatase 1 (DUSP1), a key component of the anti-inflammatory response. Stress kinases are well-describ...

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Detalhes bibliográficos
Autores: Celaya, Adelaida M., Sánchez Pérez, María Isabel, Bermúdez-Muñoz, Jose M., Rodríguez De La Rosa, Lourdes, Pintado Berninches, Laura, Perona, Rosario, Murillo-Cuesta, Silvia, Varela-Nieto, Isabel
Tipo de documento: artigo
Data de publicação:2019
País:España
Recursos:Universidad Autónoma de Madrid
Repositório:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglês
OAI Identifier:oai:repositorio.uam.es:10486/689031
Acesso em linha:http://hdl.handle.net/10486/689031
https://dx.doi.org/10.7554/eLife.39159
Access Level:Acceso aberto
Palavra-chave:Mitogen-activated
Protein kinase
Phosphatase 1
DUSP1
Medicina
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spelling Deficit of mitogen-activated protein kinase phosphatase 1 (Dusp1) accelerates progressive hearing lossCelaya, Adelaida M.Sánchez Pérez, María IsabelBermúdez-Muñoz, Jose M.Rodríguez De La Rosa, LourdesPintado Berninches, LauraPerona, RosarioMurillo-Cuesta, SilviaVarela-Nieto, IsabelMitogen-activatedProtein kinasePhosphatase 1DUSP1MedicinaMitogen-activated protein kinases (MAPK) such as p38 and the c-Jun N-terminal kinases (JNKs) are activated during the cellular response to stress signals. Their activity is regulated by the MAPK-phosphatase 1 (DUSP1), a key component of the anti-inflammatory response. Stress kinases are well-described elements of the response to otic injury and the otoprotective potential of JNK inhibitors is being tested in clinical trials. By contrast, there are no studies exploring the role of DUSP1 in hearing and hearing loss. Here we show that Dusp1 expression is age-regulated in the mouse cochlea. Dusp1 gene knock-out caused premature progressive hearing loss, as confirmed by auditory evoked responses in Dusp1–/– mice. Hearing loss correlated with cell death in hair cells, degeneration of spiral neurons and increased macrophage infiltration. Dusp1–/– mouse cochleae showed imbalanced redox status and dysregulated expression of cytokines. These data suggest that DUSP1 is essential for cochlear homeostasis in the response to stress during ageing.This work has been supported by Spanish MINECO/FEDER SAF2017-86107-R to IVN and P17-01401 (Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain) supported by FEDER funds to RP and IS-P. SM, and LR hold CIBER ISCIII researcher contracts. AMC was supported by contracts from FP7-PEOPLE-2013-IAPP TARGEAR and FEDER/CIBEREReLife Sciences PublicationsDepartamento de BioquímicaFacultad de MedicinaInstituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)Instituto de Investigación Sanitaria del Hospital Universitario de La Paz (IdiPAZ)20192019-04-02research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/689031https://dx.doi.org/10.7554/eLife.39159reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6890312026-06-23T12:46:27Z
dc.title.none.fl_str_mv Deficit of mitogen-activated protein kinase phosphatase 1 (Dusp1) accelerates progressive hearing loss
title Deficit of mitogen-activated protein kinase phosphatase 1 (Dusp1) accelerates progressive hearing loss
spellingShingle Deficit of mitogen-activated protein kinase phosphatase 1 (Dusp1) accelerates progressive hearing loss
Celaya, Adelaida M.
Mitogen-activated
Protein kinase
Phosphatase 1
DUSP1
Medicina
title_short Deficit of mitogen-activated protein kinase phosphatase 1 (Dusp1) accelerates progressive hearing loss
title_full Deficit of mitogen-activated protein kinase phosphatase 1 (Dusp1) accelerates progressive hearing loss
title_fullStr Deficit of mitogen-activated protein kinase phosphatase 1 (Dusp1) accelerates progressive hearing loss
title_full_unstemmed Deficit of mitogen-activated protein kinase phosphatase 1 (Dusp1) accelerates progressive hearing loss
title_sort Deficit of mitogen-activated protein kinase phosphatase 1 (Dusp1) accelerates progressive hearing loss
dc.creator.none.fl_str_mv Celaya, Adelaida M.
Sánchez Pérez, María Isabel
Bermúdez-Muñoz, Jose M.
Rodríguez De La Rosa, Lourdes
Pintado Berninches, Laura
Perona, Rosario
Murillo-Cuesta, Silvia
Varela-Nieto, Isabel
author Celaya, Adelaida M.
author_facet Celaya, Adelaida M.
Sánchez Pérez, María Isabel
Bermúdez-Muñoz, Jose M.
Rodríguez De La Rosa, Lourdes
Pintado Berninches, Laura
Perona, Rosario
Murillo-Cuesta, Silvia
Varela-Nieto, Isabel
author_role author
author2 Sánchez Pérez, María Isabel
Bermúdez-Muñoz, Jose M.
Rodríguez De La Rosa, Lourdes
Pintado Berninches, Laura
Perona, Rosario
Murillo-Cuesta, Silvia
Varela-Nieto, Isabel
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Bioquímica
Facultad de Medicina
Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)
Instituto de Investigación Sanitaria del Hospital Universitario de La Paz (IdiPAZ)
dc.subject.none.fl_str_mv Mitogen-activated
Protein kinase
Phosphatase 1
DUSP1
Medicina
topic Mitogen-activated
Protein kinase
Phosphatase 1
DUSP1
Medicina
description Mitogen-activated protein kinases (MAPK) such as p38 and the c-Jun N-terminal kinases (JNKs) are activated during the cellular response to stress signals. Their activity is regulated by the MAPK-phosphatase 1 (DUSP1), a key component of the anti-inflammatory response. Stress kinases are well-described elements of the response to otic injury and the otoprotective potential of JNK inhibitors is being tested in clinical trials. By contrast, there are no studies exploring the role of DUSP1 in hearing and hearing loss. Here we show that Dusp1 expression is age-regulated in the mouse cochlea. Dusp1 gene knock-out caused premature progressive hearing loss, as confirmed by auditory evoked responses in Dusp1–/– mice. Hearing loss correlated with cell death in hair cells, degeneration of spiral neurons and increased macrophage infiltration. Dusp1–/– mouse cochleae showed imbalanced redox status and dysregulated expression of cytokines. These data suggest that DUSP1 is essential for cochlear homeostasis in the response to stress during ageing.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-04-02
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/689031
https://dx.doi.org/10.7554/eLife.39159
url http://hdl.handle.net/10486/689031
https://dx.doi.org/10.7554/eLife.39159
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv eLife Sciences Publications
publisher.none.fl_str_mv eLife Sciences Publications
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301629

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