Low-dose arsenic induces a metabolic shift.
A, human fibroblasts were treated with arsenic (As) (100 nm) for 12 h. mRNA was isolated, and the transcripts of the indicated genes were determined by quantitative RT-PCR. Data are mean ± S.D. from three independent experiments. B, arsenic-treated (100 nm) fibroblasts were subjected to Western blot analysis using the indicated antibodies. C, human fibroblasts were transfected with either control RNAi (siGL2) or siHIF-1α. The cells were subjected to treatment with arsenic (100 nm) 48 h post-transfection. The cells were harvested at 12 h later for analysis of the indicated transcripts. Con, control. D and E, fibroblasts were treated with arsenic (100 nm) for 12 h and incubated with d-[1,2-13C]glucose for 15 min prior to metabolite extraction and targeted LC-MS/MS analysis. The ratio of 13C-labeled to unlabeled (12C) metabolites was measured by LC-MS/MS and is presented as mean ± S.D. over three independent samples (*, p < 0.05).