5 research outputs found
Inhibition of Histone Deacetylases Induces K+ Channel Remodeling and Action Potential Prolongation in HL-1 Atrial Cardiomyocytes
Background/Aims: Cardiac arrhythmias are triggered by environmental stimuli that may modulate expression of cardiac ion channels. Underlying epigenetic regulation of cardiac electrophysiology remains incompletely understood. Histone deacetylases (HDACs) control gene expression and cardiac integrity. We hypothesized that class I/II HDACs transcriptionally regulate ion channel expression and determine action potential duration (APD) in cardiac myocytes. Methods: Global class I/II HDAC inhibition was achieved by administration of trichostatin A (TSA). HDAC-mediated effects on K+ channel expression and electrophysiological function were evaluated in murine atrial cardiomyocytes (HL-1 cells) using real-time PCR, Western blot, and patch clamp analyses. Electrical tachypacing was employed to recapitulate arrhythmia-related effects on ion channel remodeling in the absence and presence of HDAC inhibition. Results: Global HDAC inhibition increased histone acetylation and prolonged APD90 in atrial cardiomyocytes compared to untreated control cells. Transcript levels of voltage-gated or inwardly rectifying K+ channels Kcnq1, Kcnj3 and Kcnj5 were significantly reduced, whereas Kcnk2, Kcnj2 and Kcnd3 mRNAs were upregulated. Ion channel remodeling was similarly observed at protein level. Short-term tachypacing did not induce significant transcriptional K+ channel remodeling. Conclusion: The present findings link class I/II HDAC activity to regulation of ion channel expression and action potential duration in atrial cardiomyocytes. Clinical implications for HDAC-based antiarrhythmic therapy and cardiac safety of HDAC inhibitors require further investigation
Epigenetic alterations as biomarkers in pancreatic ductal adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) prognosis remains very poor and has only marginally improved during the last decades. Epigenetic alterations have been the focus of many recent studies and offer valuable options for PDAC detection, prognosis and treatment. DNA methylation, histone modifications and microRNA (miR) level changes can be used as biomarkers. These alterations occur early in carcinogenesis and may be specific for PDAC. Additionally, epigenetic alterations can be analyzed from cell-free DNA, free-circulating nucleosomes or shed tumor cells in blood. High-throughput methods are available for miR and DNA methylation level detection. In particular, multiple promising miR level changes have been discovered. No single epigenetic biomarker that offers a sufficient specificity has been discovered yet, but patterns containing multiple independent biomarkers exist
Inhibition of Histone Deacetylases Induces K+ Channel Remodeling and Action Potential Prolongation in HL-1 Atrial Cardiomyocytes
Protéger la nature, est-ce protéger la société ?
Pourquoi s’intéresser à cette question « Protéger la nature, est-ce protéger la société ? » alors que l’idée de protection de la nature semble faire l’objet d’une approbation largement consensuelle ? Nos sociétés semblent s’être habituées d’une part à ces aires protégées aux statuts très variés et d’autre part à une nature du quotidien sans cesse aménagée par l’homme. Bien qu’il suscite d’importants conflits d’usage, ce schéma ne s’intègre-t-il pas dans un ordre social parce qu’il lui convient ? Autrement dit, protéger la nature, n’est-ce pas aussi protéger des intérêts en place, un ou des ordres établis ? N’y a-t-il pas des initiatives de préservation qui s’inscrivent en contrepoint du schéma traditionnel ? Au moment où l’avenir de la biosphère fait l’objet de nombreux débats, les changements intervenus ces dernières années dans les politiques de protection de la nature n’invalident pas l’intérêt de ces questions, bien au contraire