Redox biology, 2018-06, Vol.16, p.146-156
2018
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- Autor(en) / Beteiligte
- Titel
- Cardiomyocyte hypertrophy induced by Endonuclease G deficiency requires reactive oxygen radicals accumulation and is inhibitable by the micropeptide humanin
- Ist Teil von
- Redox biology, 2018-06, Vol.16, p.146-156
- Ort / Verlag
- Netherlands: Elsevier B.V
- Erscheinungsjahr
- 2018
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. •Endog deficiency induces cardiomyocyte hypertrophy and superoxide accumulation.•Hypertrophy induced by Endog deficiency requires ROS accumulation.•ENDOG is involved in mtDNA replication independently of ROS accumulation.•Electron Transport Chain activity is not affected by Endog deficiency.•Humanin restricts ROS accumulation and blocks cardiomyocyte growth.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2213-2317eISSN: 2213-2317DOI: 10.1016/j.redox.2018.02.021Titel-ID: cdi_doaj_primary_oai_doaj_org_article_e9f7dcc0f3da43138d4fb856b971dc9a
- Format
- –
- Schlagworte
- Animals, Apoptosis - drug effects, cardiac hypertrophy, DNA, Mitochondrial - drug effects, Endodeoxyribonucleases - deficiency, Endodeoxyribonucleases - genetics, Endodeoxyribonucleases - metabolism, ENDOG, humanin, Humans, Hypertrophy - drug therapy, Hypertrophy - enzymology, Hypertrophy - genetics, Hypertrophy - metabolism, Intracellular Signaling Peptides and Proteins - administration & dosage, Mice, Mitochondria - drug effects, Mitochondria - genetics, mitochondrial DNA, Myocytes, Cardiac - drug effects, Myocytes, Cardiac - enzymology, Myocytes, Cardiac - metabolism, Myocytes, Cardiac - pathology, Oxidation-Reduction - drug effects, Reactive Oxygen Species - metabolism, Research Paper, Signal Transduction - drug effects