RGS6 expression is sufficient to drive hepatic ATM phosphorylation in vivo and oxidative stress and cell death in hepatocytes. (A) Control and HFD-fed mice were administered vehicle or a viral construct encoding RGS6L via tail vein injection prior to initiation of the HFD (n = 3). Animals were sacrificed after 12 weeks of HFD feeding. Immunoblotting was performed to detect RGS6, pATM/ATM, and γH2AX and densitometric quantification provided. β-Actin is used as a loading control for all immunoblots. (B–D) HepaRG cells were treated with PA (400 μM, 24 h) 24 h following transfection with RGS6L. (B) CM-H2DCFDA fluorescence (n = 7) and apoptosis as measured via (C) cytoplasmic histone-associated DNA fragments (n = 7) or (D) TUNEL positive cells (n = 7). Data were analyzed by two-way ANOVA with Sidak's post-hoc test. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. ns = not significant. Data are presented as mean ± SEM.