Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage
Acetaminophen overdose is one of the leading causes of acute liver failure and liver transplantation in the Western world. Magnesium is essential in several cellular processess. The Cyclin M family is involved in magnesium transport across cell membranes. Herein, we identify that among all magnesium...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Recursos: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/296821 |
| Acesso em linha: | http://hdl.handle.net/10261/296821 |
| Access Level: | acceso abierto |
| Palavra-chave: | Gastroenterology Hepatology |
| id |
ES_bc02b04553568aea250cdacccf2bd36c |
|---|---|
| oai_identifier_str |
oai:digital.csic.es:10261/296821 |
| network_acronym_str |
ES |
| network_name_str |
España |
| repository_id_str |
|
| dc.title.none.fl_str_mv |
Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage |
| title |
Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage |
| spellingShingle |
Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage González-Recio, Irene Gastroenterology Hepatology |
| title_short |
Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage |
| title_full |
Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage |
| title_fullStr |
Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage |
| title_full_unstemmed |
Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage |
| title_sort |
Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage |
| dc.creator.none.fl_str_mv |
González-Recio, Irene Simón, Jorge Goikoetxea-Usandizaga, Naroa Serrano-Maciá, Marina Rodríguez-Agudo, Rubén Lachiondo-Ortega, Sofía Gil-Pitarch, Clàudia Fernández-Rodríguez, Carmen Castellana, Donatello Latasa, Maria U. Abecia, Leticia Anguita, Juan Delgado, Teresa C. Iruzubieta, Paula Crespo, Javier Hardy, Serge Petrov, Petar D. Jover, Ramiro Ávila, Matías A. Martín, César Schaeper, Ute Tremblay, Michel L. Dear, James W. Masson, Steven McCain, Misti Reeves, Helen L. Andrade, Raúl J. Lucena, María Isabel Buccella, Daniela Martínez-Cruz, Luis Alfonso Martínez-Chantar, María Luz |
| author |
González-Recio, Irene |
| author_facet |
González-Recio, Irene Simón, Jorge Goikoetxea-Usandizaga, Naroa Serrano-Maciá, Marina Rodríguez-Agudo, Rubén Lachiondo-Ortega, Sofía Gil-Pitarch, Clàudia Fernández-Rodríguez, Carmen Castellana, Donatello Latasa, Maria U. Abecia, Leticia Anguita, Juan Delgado, Teresa C. Iruzubieta, Paula Crespo, Javier Hardy, Serge Petrov, Petar D. Jover, Ramiro Ávila, Matías A. Martín, César Schaeper, Ute Tremblay, Michel L. Dear, James W. Masson, Steven McCain, Misti Reeves, Helen L. Andrade, Raúl J. Lucena, María Isabel Buccella, Daniela Martínez-Cruz, Luis Alfonso Martínez-Chantar, María Luz |
| author_role |
author |
| author2 |
Simón, Jorge Goikoetxea-Usandizaga, Naroa Serrano-Maciá, Marina Rodríguez-Agudo, Rubén Lachiondo-Ortega, Sofía Gil-Pitarch, Clàudia Fernández-Rodríguez, Carmen Castellana, Donatello Latasa, Maria U. Abecia, Leticia Anguita, Juan Delgado, Teresa C. Iruzubieta, Paula Crespo, Javier Hardy, Serge Petrov, Petar D. Jover, Ramiro Ávila, Matías A. Martín, César Schaeper, Ute Tremblay, Michel L. Dear, James W. Masson, Steven McCain, Misti Reeves, Helen L. Andrade, Raúl J. Lucena, María Isabel Buccella, Daniela Martínez-Cruz, Luis Alfonso Martínez-Chantar, María Luz |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Ministerio de Ciencia, Innovación y Universidades (España) Agencia Estatal de Investigación (España) European Commission Comisión Asesora de Investigación Científica y Técnica, CAICYT (España) Ministerio de Economía y Competitividad (España) Asociación Española Contra el Cáncer Fundación Científica Asociación Española Contra el Cáncer Fundación la Caixa Fundación BBVA European Joint Programme on Rare Diseases Instituto de Salud Carlos III National Institutes of Health (US) Newcastle Biobanks European Commission Cancer Research UK Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
Gastroenterology Hepatology |
| topic |
Gastroenterology Hepatology |
| description |
Acetaminophen overdose is one of the leading causes of acute liver failure and liver transplantation in the Western world. Magnesium is essential in several cellular processess. The Cyclin M family is involved in magnesium transport across cell membranes. Herein, we identify that among all magnesium transporters, only Cyclin M4 expression is upregulated in the liver of patients with acetaminophen overdose, with disturbances in magnesium serum levels. In the liver, acetaminophen interferes with the mitochondrial magnesium reservoir via Cyclin M4, affecting ATP production and reactive oxygen species generation, further boosting endoplasmic reticulum stress. Importantly, Cyclin M4 mutant T495I, which impairs magnesium flux, shows no effect. Finally, an accumulation of Cyclin M4 in endoplasmic reticulum is shown under hepatoxicity. Based on our studies in mice, silencing hepatic Cyclin M4 within the window of 6 to 24 h following acetaminophen overdose ingestion may represent a therapeutic target for acetaminophen overdose induced liver injury. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2023 2023 |
| 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/10261/296821 |
| url |
http://hdl.handle.net/10261/296821 |
| 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# info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-117116RB-I00 info:eu-repo/grantAgreement/MINECO//BFU2013-47531-R info:eu-repo/grantAgreement/MINECO//BFU2016-77408-R info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-109055RB-I00 info:eu-repo/grantAgreement/AEI//RYC2020-029316-I info:eu-repo/grantAgreement/AEI//RTC2019-007125-1 info:eu-repo/grantAgreement/MINECO//SEV-2016-0644 info:eu-repo/grantAgreement/AEI//BES-2017-080435 https://doi.org/10.1038/s41467-022-34262-0 Sí |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Nature Publishing Group |
| publisher.none.fl_str_mv |
Nature Publishing Group |
| 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 |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
|
| _version_ |
1869418076187918336 |
| spelling |
Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damageGonzález-Recio, IreneSimón, JorgeGoikoetxea-Usandizaga, NaroaSerrano-Maciá, MarinaRodríguez-Agudo, RubénLachiondo-Ortega, SofíaGil-Pitarch, ClàudiaFernández-Rodríguez, CarmenCastellana, DonatelloLatasa, Maria U.Abecia, LeticiaAnguita, JuanDelgado, Teresa C.Iruzubieta, PaulaCrespo, JavierHardy, SergePetrov, Petar D.Jover, RamiroÁvila, Matías A.Martín, CésarSchaeper, UteTremblay, Michel L.Dear, James W.Masson, StevenMcCain, MistiReeves, Helen L.Andrade, Raúl J.Lucena, María IsabelBuccella, DanielaMartínez-Cruz, Luis AlfonsoMartínez-Chantar, María LuzGastroenterologyHepatologyAcetaminophen overdose is one of the leading causes of acute liver failure and liver transplantation in the Western world. Magnesium is essential in several cellular processess. The Cyclin M family is involved in magnesium transport across cell membranes. Herein, we identify that among all magnesium transporters, only Cyclin M4 expression is upregulated in the liver of patients with acetaminophen overdose, with disturbances in magnesium serum levels. In the liver, acetaminophen interferes with the mitochondrial magnesium reservoir via Cyclin M4, affecting ATP production and reactive oxygen species generation, further boosting endoplasmic reticulum stress. Importantly, Cyclin M4 mutant T495I, which impairs magnesium flux, shows no effect. Finally, an accumulation of Cyclin M4 in endoplasmic reticulum is shown under hepatoxicity. Based on our studies in mice, silencing hepatic Cyclin M4 within the window of 6 to 24 h following acetaminophen overdose ingestion may represent a therapeutic target for acetaminophen overdose induced liver injury.This work was supported by Ministerio de Ciencia, Innovación y Universidades MICINN: PID2020-117116RB-I00 integrado en el Plan Estatal de Investigación Cientifica y Técnica y Innovación, cofinanciado con Fondos FEDER (to MLM-C), Ministerio de Ciencia e Innovación CONSOLIDER-INGENIO 2010 Program Grant CSD2008-00005 (to LAM-C); Spanish Ministry of Economy and Competitiveness Grant BFU2013-47531-R, BFU2016-77408-R, PID2019-109055RB-100 (to L.A.M.-C.) (MINECO/FEDER, UE); Asociación Española contra el Cáncer (MLM-C, TC-D), Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation) Rare Tumor Calls 2017 (to M.L.M.-C.), La Caixa Foundation Program (to M.L.M.-C.), Fundacion BBVA UMBRELLA project (to M.L.M.-C.), Ayuda RYC2020-029316-I financiada por MICIN/AEI/10.13039/501100011033 (to TC-D), Plataforma de Investigación Clínica-SCReN (PT17 0017 0020) (to M.I.-L.), programa retos RTC2019-007125-1 (to M.L.M.-C, J.S.), Proyectos Investigacion en Salud DTS20/00138 (to M.L.M.-C., J.S), ERA-Net E-Rare EJP RD Joint Translational Call for Rare Diseases FIGHT-CNNM2 (EJPRD19-040) and from Instituto Carlos III, Spain (REF G95229142) (to L.A.M.-C.), US National Institutes of Health under grant CA217817 (to D.B.), Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III. We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644) and PhD fellowship from MINECO (REF BES-2017-080435) awarded to I.G.-R. The collection and storage of patients tissues was supported by the Newcastle Biomedicine Biobank and the European Community’s Seventh Framework Programme (FP7/2001–2013) and Cancer Research UK awards Cancer Research UK grants C18342/A23390; C9380/A18084 and C9380/A26813.Peer reviewedNature Publishing GroupMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)European CommissionComisión Asesora de Investigación Científica y Técnica, CAICYT (España)Ministerio de Economía y Competitividad (España)Asociación Española Contra el CáncerFundación Científica Asociación Española Contra el CáncerFundación la CaixaFundación BBVAEuropean Joint Programme on Rare DiseasesInstituto de Salud Carlos IIINational Institutes of Health (US)Newcastle BiobanksEuropean CommissionCancer Research UKConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/296821reponame: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#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-117116RB-I00info:eu-repo/grantAgreement/MINECO//BFU2013-47531-Rinfo:eu-repo/grantAgreement/MINECO//BFU2016-77408-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-109055RB-I00info:eu-repo/grantAgreement/AEI//RYC2020-029316-Iinfo:eu-repo/grantAgreement/AEI//RTC2019-007125-1info:eu-repo/grantAgreement/MINECO//SEV-2016-0644info:eu-repo/grantAgreement/AEI//BES-2017-080435https://doi.org/10.1038/s41467-022-34262-0Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2968212026-05-22T06:33:51Z |
| score |
15.812429 |