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Impaired PARP activity in response to the β-adrenergic receptor agonist isoproterenol

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2018

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Bazylianska, Viktoriia
Schäfer, Nadine

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https://doi.org/10.1016/j.tiv.2018.02.001
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Toxicology in Vitro. 2018, 50, pp. 29-39. ISSN 0887-2333. eISSN 1879-3177. Available under: doi: 10.1016/j.tiv.2018.02.001

Zusammenfassung

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.

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570 Biowissenschaften, Biologie

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Isoproterenol, Chronic stress, PARP, DNA strand breaks, DNA repair

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ISO 690THOMAS, Mara, Philipp PALOMBO, Tamara SCHUHMACHER, Gudrun VON SCHEVEN, Viktoriia BAZYLIANSKA, Judy FIERES, Nadine SCHÄFER, Alexander BÜRKLE, Maria MORENO-VILLANUEVA, 2018. Impaired PARP activity in response to the β-adrenergic receptor agonist isoproterenol. In: Toxicology in Vitro. 2018, 50, pp. 29-39. ISSN 0887-2333. eISSN 1879-3177. Available under: doi: 10.1016/j.tiv.2018.02.001
BibTex
@article{Thomas2018-02-10Impai-41787,
  year={2018},
  doi={10.1016/j.tiv.2018.02.001},
  title={Impaired PARP activity in response to the β-adrenergic receptor agonist isoproterenol},
  volume={50},
  issn={0887-2333},
  journal={Toxicology in Vitro},
  pages={29--39},
  author={Thomas, Mara and Palombo, Philipp and Schuhmacher, Tamara and von Scheven, Gudrun and Bazylianska, Viktoriia and Fieres, Judy and Schäfer, Nadine and Bürkle, Alexander and Moreno-Villanueva, Maria}
}
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