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dc.contributor.authorBlasco, Natividad
dc.contributor.authorCamara, Yolanda
dc.contributor.authorNunez, Estefania 
dc.contributor.authorBea, Aida
dc.contributor.authorBares, Gisel
dc.contributor.authorForne, Carles
dc.contributor.authorRuiz-Meana, Marisol
dc.contributor.authorGiron, Cristina
dc.contributor.authorBarba, Ignasi
dc.contributor.authorGarcia-Arumi, Elena
dc.contributor.authorGarcia-Dorado, David
dc.contributor.authorVazquez, Jesus 
dc.contributor.authorMarti, Ramon
dc.contributor.authorLlovera, Marta
dc.contributor.authorSanchis, Daniel
dc.date.accessioned2018-10-26T07:59:28Z
dc.date.available2018-10-26T07:59:28Z
dc.date.issued2018
dc.identifierISI:000446404400014
dc.identifier.citationRedox Biol. 2018; 16:146-156
dc.identifier.issn2213-2317
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6544
dc.description.abstractThe endonuclease G gene (Endog), which codes for a mitochondrial nuclease, was identified as a determinant of cardiac hypertrophy. How ENDOG controls cardiomyocyte growth is still unknown. Thus, we aimed at finding the link between ENDOG activity and cardiomyocyte growth. Endog deficiency induced reactive oxygen species (ROS) accumulation and abnormal growth in neonatal rodent cardiomyocytes, altering the AKT-GSK3 beta and Class-II histone deacethylases (HDAC) signal transduction pathways. These effects were blocked by ROS scavengers. Lack of ENDOG reduced mitochondrial DNA (mtDNA) replication independently of ROS accumulation. Because mtDNA encodes several subunits of the mitochondrial electron transport chain, whose activity is an important source of cellular ROS, we investigated whether Endog deficiency compromised the expression and activity of the respiratory chain complexes but found no changes in these parameters nor in ATP content. MtDNA also codes for humanin, a micropeptide with possible metabolic functions. Nanomolar concentrations of synthetic humanin restored normal ROS levels and cell size in Endog-deficient cardiomyocytes. These results support the involvement of redox signaling in the control of cardiomyocyte growth by ENDOG and suggest a pathway relating mtDNA content to the regulation of cell growth probably involving humanin, which prevents reactive oxygen radicals accumulation and hypertrophy induced by Endog deficiency.
dc.description.sponsorshipThis work was supported by Grant SAF2013-44942R from the Ministerio de Economia y Competitividad (MINECO) to DS, Grant 20153810 from Fundacio La Marato de TV3 to DS, Program ``Redes Tematicas de Investigacion Cooperativa en Salud´´ (RETICS) Grants RD12/0042/0035, RD12/0042/0056 and RD12/0042/0021, Red de Investigacion Cardiovascular (RIC) from the Institute de Salud Carlos-III (ISCIII) to DS, DG-D and JV, Grant 2009SGR-346 from the Agencia de Gestic d'Ajuts Universitaris i de Recerca (AGAUR) from the Government of Catalonia to DS. AB is supported by Fundacio La Marato de TV3 and GB is supported by a predoctoral contract from the Universitat de Lleida.
dc.language.isoeng
dc.publisherElsevier
dc.relation.isversionofPublisher's version
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectcardiac hypertrophy
dc.subjectENDOG
dc.subjectmitochondrial DNA
dc.subjecthumanin
dc.subjectMITOCHONDRIAL-DNA REPLICATION
dc.subjectMEF2 TRANSCRIPTION FACTOR
dc.subjectCARDIAC-HYPERTROPHY
dc.subjectOXIDATIVE STRESS
dc.subjectDEPENDENT ACTIVATION
dc.subjectTRANSLATION
dc.subjectISCHEMIA
dc.subjectPATHWAY
dc.subjectDEATH
dc.subjectHDAC4
dc.titleCardiomyocyte hypertrophy induced by Endonuclease G deficiency requires reactive oxygen radicals accumulation and is inhibitable by the micropeptide humanin
dc.typeArtículo
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.identifier.pubmedID29502044
dc.format.volume16
dc.format.page146-156
dc.identifier.doi10.1016/j.redox.2018.02.021
dc.contributor.funderMinisterio de Economia y Competitividad (España)
dc.contributor.funderFundacio la Marato
dc.contributor.funderInstituto de Salud Carlos III - ISCIII
dc.contributor.funderRed de Investigacion Cardiovascular (España)
dc.contributor.funderGeneralitat de Catalunya
dc.contributor.funderCentro de Investigación Biomedica en Red - CIBER
dc.contributor.funderUniversitat de Lleida
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1016/j.redox.2018.02.021
dc.identifier.journalRedox Biology
dc.repisalud.orgCNICCNIC::Grupos de investigación::Proteómica cardiovascular
dc.repisalud.institucionCNIC
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
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