| http://purl.uniprot.org/citations/30898999 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30898999 | http://www.w3.org/2000/01/rdf-schema#comment | "Atrial fibrillation (AF) is the most common clinical tachyarrhythmia with a strong tendency to progress in time. AF progression is driven by derailment of protein homeostasis, which ultimately causes contractile dysfunction of the atria. Here we report that tachypacing-induced functional loss of atrial cardiomyocytes is precipitated by excessive poly(ADP)-ribose polymerase 1 (PARP1) activation in response to oxidative DNA damage. PARP1-mediated synthesis of ADP-ribose chains in turn depletes nicotinamide adenine dinucleotide (NAD+), induces further DNA damage and contractile dysfunction. Accordingly, NAD+ replenishment or PARP1 depletion precludes functional loss. Moreover, inhibition of PARP1 protects against tachypacing-induced NAD+ depletion, oxidative stress, DNA damage and contractile dysfunction in atrial cardiomyocytes and Drosophila. Consistently, cardiomyocytes of persistent AF patients show significant DNA damage, which correlates with PARP1 activity. The findings uncover a mechanism by which tachypacing impairs cardiomyocyte function and implicates PARP1 as a possible therapeutic target that may preserve cardiomyocyte function in clinical AF."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41467-019-09014-2"xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/author | "Hu X."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/author | "Li J."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/author | "Liu J."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/author | "Zhang D."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/author | "de Vries A.A.F."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/author | "Henning R.H."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/author | "Wiersma M."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/author | "Brundel B.J.J.M."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/author | "van Roon A.M."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/author | "Pijnappels D.A."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/author | "Hoogstra-Berends F."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/author | "Baks-Te Bulte L."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/author | "Lanters E.A.H."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/author | "Malik N.U."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/author | "Tolouee M."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/author | "de Groot N.M.S."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/author | "van Marion D.M.S."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/name | "Nat Commun"xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/pages | "1307"xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/title | "DNA damage-induced PARP1 activation confers cardiomyocyte dysfunction through NAD+ depletion in experimental atrial fibrillation."xsd:string |
| http://purl.uniprot.org/citations/30898999 | http://purl.uniprot.org/core/volume | "10"xsd:string |