Impaired PARP activity in response to the ß-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 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 ß-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 ß-adrenergic stimulation and PARP-1.

Bayesian informed evidence against modulation of androstadienone-effects by genotypic receptor variants and participant sex: A study assessing Stroop interference control, mood and olfaction.

The androgen derivative androstadienone (AND) is present in human sweat and may act as human chemosignal. Though effects of AND have been reported with respect to emotional and cognitive processes, results have been highly inconsistent. For this reason, it is likely that AND-action is dependent on modulatory factors. Here we wanted to specifically investigate the impact of genotypic variations of the AND-receptor OR7D4, as well as the influence of participant sex and concomitant hormonal fluctuations on AND-action during emotional interference processing, olfactory performance and mood assessments. To this end 80 healthy individuals (women taking oral contraceptives; naturally cycling women measured during the luteal phase and men) were tested twice on two consecutive days (AND vs. placebo exposure) with an emotional Stroop task. Also, olfactory performance and mood was assessed. Participants provided saliva samples to measure testosterone, progesterone and estradiol and a blood sample to assess genotypic variations of the AND-receptor OR7D4. We found a small task-dependent reduction of overall error rates under AND but no modulation of effects by genetic variation or group (female OC, female NC, male) with respect to olfactory performance and mood. Additional analyses with help of Bayesian statistics gave strong evidence in favor of specific null hypotheses suggesting that the action of AND was not modulated by either genotypic variations or sex of participants with respect to interference control (bias indices), olfactory self-reports and mood parameters. Additional effects of AND in connection with hormonal fluctuations are reported.