ATO-mediated apoptosis is regulated by Ca++/calpain-1/caspase-12-mediated apoptosis. (A) Line graph showing intracellular Ca++ release from ATO-treated Raw 264.7 cells at 14 h. Fluorescence intensity was recorded at excitation wavelength 494 nm and emission wavelength 516 nm using a microplate reader and expressed as mean of relative fluorescence unit (RFU). (B); (B–I) Western blot analysis for p-IP3R, calpain-1, cleaved caspase-12, and cleaved caspase-3 proteins in lysates prepared from ATO-treated (1 and 2 μM for 24 h) Raw 264.7 cells. (B–II) Histogram representing the densitometry analysis of western blots. (C) Western blot analysis for calpain-1, cleaved caspase-12 and cleaved caspase-3 proteins in ATO-treated Raw 264.7 cell lysate. These cells were pretreated with calcium chelator, Quin2 (20 μM for 3 h) or calpain inhibitor, PD150606 (10 μM for 3 h) or IP3R inhibitor, 2-APB (20 μM, 6 h). In these experiments calcium ionophore (cal. iono.), (2 μM for 3 h) was used as positive control to address whether the effects are indeed Ca++ regulated. Histograms representing the densitometry analysis of western blots. Data are expressed as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 compared to control. #P < 0.05, ##P < 0.01, compared to ATO-treated group.