Portal de investigación
Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage.
Fecha de publicación:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Gonzalez-Recio, Irene
- Simon, Jorge
- Goikoetxea-Usandizaga, Naroa
- Serrano-Macia, Marina
- Mercado-Gomez, Maria
- Rodriguez-Agudo, Ruben
- Lachiondo-Ortega, Sofia
- Gil-Pitarch, Claudia
- Fernandez-Rodriguez, Carmen
- Castellana, Donatello
- Latasa, Maria U.
- Abecia, Leticia
- Anguita, Juan
- Delgado, Teresa C.
- Iruzubieta, Paula
- Crespo, Javier
- Hardy, Serge
- Petrov, Petar D.
- Avila, Matias A.
- Martin, Cesar
- Schaeper, Ute
- Tremblay, Michel L.
- Dear, James W.
- Masson, Steven
- McCain, Misti Vanette
- Reeves, Helen L.
- Andrade, Raul J.
- Lucena, M. Isabel
- Buccella, Daniela
- Martinez-Cruz, Luis Alfonso
- Martinez-Chantar, Maria L.
Grupos
Abstract
Drug induced liver injury (DILI) is an important cause acute liver failure. Here the authors report that serum Mg2+ serum levels decrease in patients with DILI as well as in preclinical animal models treated with acetaminophen overdose, and that early intervention targeting the Mg2+ transporter Cyclin M4 may be beneficial for acetaminophen overdose in preclinical models. 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.
Datos de la publicación
- ISSN/ISSNe:
- 2041-1723, 2041-1723
- Tipo:
- Article
- Páginas:
- 6816-6816
- Factor de Impacto:
- 4,846 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
NATURE COMMUNICATIONS NATURE PUBLISHING GROUP
Citas Recibidas en Web of Science: 12
Documentos
- No hay documentos
Filiaciones
Keywords
- INTRACELLULAR MAGNESIUM; N-ACETYLCYSTEINE; HEPATOTOXICITY; MITOCHONDRIAL; INHIBITION; CALCIUM; MG2+; MICE; THAPSIGARGIN; INFLAMMATION
Proyectos asociados
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Investigador Principal: JOSÉ VICENTE CASTELL RIPOLL
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LINTOP
Investigador Principal: JOSÉ VICENTE CASTELL RIPOLL
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Investigador Principal: RAMIRO JOVER ATIENZA
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Investigador Principal: RAMIRO JOVER ATIENZA
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Investigador Principal: RAMIRO JOVER ATIENZA
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Nuevos mecanismos y biomarcadores diagnósticos en la colestasis iatrogénica.
Investigador Principal: RAMIRO JOVER ATIENZA
PI17/01089 . INSTITUTO DE SALUD CARLOS III . 2018
Susceptibility factors and non-invasive biomarkers for liver steatosis induced by valproate in pediatric epileptic patients.
Investigador Principal: RAMIRO JOVER ATIENZA
PI20/00690 . INSTITUTO DE SALUD CARLOS III . 2021
YO INVESTIGO RAMIRO JOVER
Investigador Principal: RAMIRO JOVER ATIENZA
INVEST/2022/76 . CONSELLERIA DE INNOVACIÓN, UNIVERSIDADES, CIENCIA Y SOCIEDAD DIGITAL . 2022
Cita
Gonzalez I,Simon J,Goikoetxea N,Serrano M,Mercado M,Rodriguez R,Lachiondo S,Gil C,Fernandez C,Castellana D,Latasa MU,Abecia L,Anguita J,Delgado TC,Iruzubieta P,Crespo J,Hardy S,Petrov PD,Jover R,Avila MA,Martin C,Schaeper U,Tremblay ML,Dear JW,Masson S,McCain MV,Reeves HL,Andrade RJ,Lucena MI,Buccella D,Martinez LA,Martinez ML. Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage. Nat Commun. 2022. 13. (1):p. 6816-6816. IF:16,600. (1).