Fig. 7.

The activation of HIF transcription factors by Mn is a homeostatic protective response against Mn toxicity. (A) Inductively coupled plasma mass spectrometry analyses to measure intracellular metal levels in HepG2 cells stably infected with scramble shRNA (sequence 2) or HIF1-β/ARNT shRNA (sequence 1) and treated with or without 125 µM Mn for 16 h. n = 3. Mean ± SE, *P < 0.05 by two-way ANOVA (shRNA and Mn treatment as independent variables) and Sidak’s post hoc test for indicated comparisons; n.s., not significant. (B) Cell viability assays in scramble (sequence 2) or HIF1-β/ARNT shRNA (sequence 1)-infected HepG2 cells treated with 0, 0.5, or 1 mM Mn for 16 h. Viability of scramble or ARNT shRNA-infected cells that did not receive Mn was separately normalized to 100. n = 3. Mean ± SE, *P < 0.05 by two-way ANOVA (shRNA and Mn treatment as independent variables) and Sidak’s post hoc test for comparisons between infection conditions at each Mn dose.