DNA damage-induced PARP1 activation confers cardiomyocyte dysfunction through NAD⁺ depletion in experimental atrial fibrillation.

ABSTRACT: 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 s

SUBMITTER: Zhang D 

PROVIDER: S-EPMC6428932 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature