Fig. 8

Irradiation-induced DNA damage results in PARP1 activation, NAD⁺ reduction and contractile dysfunction in HL-1 cardiomyocytes. a Representative Western blot of PAR and γH2AX in control (CTL) and irradiated (IR) HL-1 cardiomyocytes treated either with vehicle (DMSO) or ABT-888. b–d Quantified data of Western blot in a, showing significant increase in PAR and γH2AX levels, indicating PARP1 activation and presence of DNA damage, respectively, due to IR. ABT-888 pretreatment protected against PAR induction. ^*P < 0.05, ^**P < 0.01 vs. CTL. n = 2 independent experiments. No significant difference was found in the amount of PARP1. e Relative NAD⁺ levels in CTL and IR HL-1 cardiomyocytes. IR resulted in reduction in NAD⁺ levels, which was prevented by ABT-888 pretreatment. ^*P < 0.05 vs. CTL treated with vehicle DMSO, ^#P < 0.05 vs. IR treated with vehicle DMSO, n = 4 independent experiments for CTL DMSO, n = 7 independent experiments for IR DMSO, n = 6 independent experiments for IR ABT-888. f Quantified CaT amplitude in CTL or IR HL-1 cardiomyocytes pretreated with ABT-888 (3 mM) or vehicle (CTL). ABT-888 protected against IR-induced CaT loss. ^**P < 0.01 vs. CTL DMSO; ^###P < 0.0001 vs. IR DMSO, n = 18 cardiomyocytes for CTL DMSO, n = 37 for IR DMSO, n = 16 for CTL ABT-888, n = 34 for 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