Impact of Cadmium on Intracellular Zinc Levels in HepG2 Cells: Quantitative Evaluations and Molecular Effects

Figure 5

Overview of cellular and molecular effects of 10 μM Cd in HepG2 cells. Cd enters the cells through aspecific sites. Intracellular Cd accumulation determines an increase of labile zinc, a known proliferation signal, and second messenger. The replacement of Zn with Cd in the zinc proteome [18] is the hypothetical process underlying the above described mechanism. Genes (Snail, MET, TGF-βR, and Rac/cdc42) involved in the loss of cell adherence and also comprised in the mechanism of epithelial-mesenchymal transition are disregulated. MicroRNAs (miR-34a, miR-200a) with tumor-suppressor functions are downregulated. Cd-exposed HepG2 cells have a nonfunctional p53 [19] that along with miR-34 downregulation represents the disregulated axis in Snail1-dependent epithelial-mesenchymal transition [20].