2026-04-29T16:55:56Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/65442024-09-27T09:47:24Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc 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 author 2018 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. 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 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