Fig. 9

Irradiation-induced DNA damage results in PARP1 activation, NAD⁺ reduction and contractile dysfunction in rat atrial cardiomyocytes. a Representative Western blot showing PAR and γH2AX levels due to irradiation (IR) with and without ABT-888 pretreatment. b–d Quantified data of Western blot in a, showing significant increase in PAR and γH2AX levels, indicating PARP activation and presence of DNA damage, respectively, due to IR. ABT-888 pretreatment protected against PAR induction. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001 vs. control nonirradiated (CTL) rat atrial cardiomyocytes treated with vehicle DMSO. ^##P < 0.01 vs. IR treated with vehicle DMSO, n = 2 independent experiments. No significant difference was found in the amount of PARP1. e Relative NAD⁺ levels in CTL and IR rat atrial cardiomyocytes treated with DMSO or ABT. IR resulted in reduction in NAD⁺ levels which was prevented by ABT-888 pretreatment *P < 0.05 vs. CTL treated with vehicle DMSO, ^##P < 0.01 vs. IR treated with vehicle DMSO, n = 3 independent experiments. f Quantified CaT amplitude in CTL or IR rat atrial cardiomyocytes pretreated with ABT-888 or vehicle (CTL). ABT-888 protected against IR-induced CaT loss. ^**P < 0.01 vs. CTL DMSO; ^#P < 0.05 vs. IR DMSO, n = 11 atrial cardiomyocytes for CTL DMSO, n = 14 for CTL ABT-888, n = 12 for IR DMSO and IR ABT-888. Data are all expressed as mean ± s.e.m. Individual group mean differences were evaluated with the two-tailed Student’s t test