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Título:
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Cardiomyocyte hypertrophy induced by Endonuclease G deficiency requires reactive oxygen radicals accumulation and is inhibitable by the micropeptide humanin.
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Autor/a:
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Blasco Angulo, Natividad; Cámara, Yolanda; Núñez, Estefanía; Beà, Aida; Barés Junqué, Gisel; Forné Izquierdo, Carles; Ruiz Meana, Marisol; Girón, Cristina; Barba, Ignasi; García Arumí, Elena; García Dorado, David; Vázquez, Jesús; Martí, Ramón; Llovera i Tomàs, Marta; Sanchis, Daniel
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Notas:
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The 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-GSK3β 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.
This work was supported by Grant SAF2013–44942R from the Ministerio de Economía y Competitividad (MINECO) to DS, Grant 20153810 from Fundació La Marató de TV3 to DS, Program “Redes Temáticas de Investigación Cooperativa en Salud” (RETICS) Grants
RD12/0042/0035, RD12/0042/0056 and RD12/0042/0021, Red de Investigación Cardiovascular (RIC) from the Instituto de Salud Carlos-III (ISCIII) to DS, DG-D and JV, Grant 2009SGR-346 from the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) from the Government of Catalonia to DS. AB is supported by Fundació La Marató de TV3 and GB is supported by a predoctoral contract from the Universitat de Lleida. |
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Materia(s):
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-Cardiac hypertrophy
-ENDOG
-Mitochondrial DNA
-Humanin |
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Derechos:
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cc-by-nc-nd, (c) Blasco et al., 2018
http://creativecommons.org/licenses/by-nc-nd/3.0/es
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Tipo de documento:
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Artículo
Artículo - Versión aceptada |
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Editor:
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Elsevier
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Compartir:
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