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Impaired PARP activity in response to the β-adrenergic receptor agonist isoproterenol
Psychological stress has been associated with DNA damage, thus increasing the risk of numerous diseases including cancer. Here, we investigate the effect of acute and chronic stress on poly(ADP-ribose) polymerase-1 (PARP-1), a sensor of DNA damage and DNA repair initiator. In order to mimic the chro...
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Published in: | Toxicology in vitro 2018-08, Vol.50, p.29-39 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Psychological stress has been associated with DNA damage, thus increasing the risk of numerous diseases including cancer. Here, we investigate the effect of acute and chronic stress on poly(ADP-ribose) polymerase-1 (PARP-1), a sensor of DNA damage and DNA repair initiator. In order to mimic the chronic release of epinephrine, human peripheral blood mononuclear cells (PBMCs) were treated repeatedly with the sympathomimetic drug isoproterenol. We found significant induction of DNA strand breaks that remained unrepaired 24 h after ex vivo incubation. Isoproterenol-induced DNA strand breaks could be partially prevented by pre-treatment with the β-adrenergic receptor antagonist propranolol. Furthermore, the level of PARP-1 protein and PARP activity decreased and the levels of the PARP substrate nicotinamide adenine dinucleotide (NAD+) and of adenosine triphosphate (ATP), necessary to replenish NAD+ pools, were lowered by isoproterenol treatment. In conclusion our data provide novel insights into the mechanisms of isoproterenol-induced genotoxicity linking β-adrenergic stimulation and PARP-1.
•Increase of residual DNA strand breaks after isoproterenol treatment.•Isoproterenol affects PARP-1 protein and activity.•Isoproterenol-mediated decrease of NAD+ and ATP |
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ISSN: | 0887-2333 1879-3177 |
DOI: | 10.1016/j.tiv.2018.02.001 |