2026-04-29T16:55:57Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/65442024-09-27T09:47:24Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Blasco, Natividad
author
Camara, Yolanda
author
Nunez, Estefania
author
Bea, Aida
author
Bares, Gisel
author
Forne, Carles
author
Ruiz-Meana, Marisol
author
Giron, Cristina
author
Barba, Ignasi
author
Garcia-Arumi, Elena
author
Garcia-Dorado, David
author
Vazquez, Jesus
author
Marti, Ramon
author
Llovera, Marta
author
Sanchis, Daniel
funder
Ministerio de Economía y Competitividad (España)
funder
Fundación La Marató TV3
funder
Instituto de Salud Carlos III
funder
Centro de Investigación Biomédica en Red - CIBERCV (Enfermedades Cardiovasculares)
funder
Government of Catalonia (España)
funder
Centro de Investigación Biomedica en Red - CIBER
funder
University of Lleida (España)
2018-10-26T07:59:28Z
2018-10-26T07:59:28Z
2018
Redox Biol. 2018; 16:146-156
10.1016/j.redox.2018.02.021
2213-2317
Redox Biology
29502044
http://hdl.handle.net/20.500.12105/6544
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-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.
eng
Cardiac hypertrophy
ENDOG
Mitochondrial DNA
Humanin
MITOCHONDRIAL-DNA REPLICATION
MEF2 TRANSCRIPTION FACTOR
CARDIAC-HYPERTROPHY
OXIDATIVE STRESS
DEPENDENT ACTIVATION
TRANSLATION
ISCHEMIA
PATHWAY
DEATH
HDAC4
Cardiomyocyte hypertrophy induced by Endonuclease G deficiency requires reactive oxygen radicals accumulation and is inhibitable by the micropeptide humanin
journal article
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CardiomyocyteHypertrophyInducedEndonuclease_2018.pdf
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CardiomyocyteHypertrophyInducedEndonuclease_2018_suppl1.pdf
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CardiomyocyteHypertrophyInducedEndonuclease_2018.pdf.txt
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CardiomyocyteHypertrophyInducedEndonuclease_2018_suppl1.pdf.txt