title: High concentrations of H2O2 trigger hypertrophic cascade and phosphatase and tensin homologue (PTEN) glutathionylation in H9c2 cardiomyocytes.
abstract: Cardiac hypertrophy occurs in response to different stimuli and is mainly characterized by an enlargement of cardiomyocyte size. During hypertrophy, cardiomyocytes undergo not only radical changes of the cellular architecture but also activation of signaling cascades that counteract the atrophy genes. Experimental studies highlighted that chronic low concentrations of H2O2, induce a hypertrophic phenotype, while higher levels of H2O2 promote apoptosis. In this study, we explored the early and long-term hypertrophic effects of high concentrations of H2O2 on H9c2 rat cardiomyocytes. We found that 2-h stimulation with 200μM H2O2 caused an early dramatic reduction of cell viability, accompanied, 5-days later, by increased cell size and up-regulation of atrial natriuretic peptide transcription. This hypertrophic phenotype is associated to increased Akt phosphorylation and a consequent reduction of the FOXO3a and atrogin-1 gene expression. Moreover, we observed that H2O2 caused the overexpression of miR-212/miR-132 cluster concomitantly to a down-regulation of PTEN transcript without changes in its protein expression. Noteworthy, we found that the treatment of cardiomyocytes with H2O2 further led to an increase of oxidized glutathione and glutathionylation of proteins, including PTEN. In conclusion, our results permit to reconstruct the molecular cascade triggering the cardiomyocyte hypertrophy upon high concentrations of H2O2.
authors.affiliation: Liver Research Unit, "Bambino Gesù" Children's Hospital and IRCCS, Viale San Paolo 15, 00146 Rome, Italy. Electronic address: nadia.panera@opbg.net.
authors.forename: Nadia
authors.initials: N
authors.lastname: Panera
authors.affiliation: Liver Research Unit, "Bambino Gesù" Children's Hospital and IRCCS, Viale San Paolo 15, 00146 Rome, Italy. Electronic address: daniela.gnani@opbg.net.
authors.forename: Daniela
authors.initials: D
authors.lastname: Gnani
authors.affiliation: Neuromuscular and Neurodegenerative Unit, "Bambino Gesù" Children's Hospital and IRCCS, Viale San Paolo 15, 00146 Rome, Italy. Electronic address: emanuela.piermarini@opbg.net.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Piermarini
authors.affiliation: Microscopy Unit, "Bambino Gesù" Children's Hospital and IRCCS, Viale San Paolo 15, 00146 Rome, Italy. Electronic address: stefania.petrini@opbg.net.
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrini
authors.affiliation: Neuromuscular and Neurodegenerative Unit, "Bambino Gesù" Children's Hospital and IRCCS, Viale San Paolo 15, 00146 Rome, Italy. Electronic address: enrico.bertini@opbg.net.
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.affiliation: Liver Research Unit, "Bambino Gesù" Children's Hospital and IRCCS, Viale San Paolo 15, 00146 Rome, Italy. Electronic address: valerio.nobili@opbg.net.
authors.forename: Valerio
authors.initials: V
authors.lastname: Nobili
authors.affiliation: Laboratory of Biochemistry, "Bambino Gesù" Children's Hospital and IRCCS, Viale San Paolo 15, 00146 Rome, Italy. Electronic address: anna.pastore@opbg.net.
authors.forename: Anna
authors.initials: A
authors.lastname: Pastore
authors.affiliation: Neuromuscular and Neurodegenerative Unit, "Bambino Gesù" Children's Hospital and IRCCS, Viale San Paolo 15, 00146 Rome, Italy. Electronic address: fiorella.piemonte@opbg.net.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Piemonte
authors.affiliation: Liver Research Unit, "Bambino Gesù" Children's Hospital and IRCCS, Viale San Paolo 15, 00146 Rome, Italy. Electronic address: anna.alisi@opbg.net.
authors.forename: Anna
authors.initials: A
authors.lastname: Alisi
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction / Q000235:genetics
chemical_list: D006861:Hydrogen Peroxide; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat; D005978:Glutathione
keywords: Cardiomyocytes; Hydrogen peroxide; Hypertrophy; Pten