Effects of Exogenous Zinc on the Cellular Zinc Distribution and Cell Cycle of A549 Cells

Abstract

As the second most abundant transition metal in humans, zinc plays essential roles in normal cellular biological functions, including metabolism, signalling, proliferation, gene expression and apoptosis. We use ZnSO₄ as a stressor in this study to investigate for the first time the effects of exogenous Zn²⁺ on both the cellular distribution of zinc and zinc-related proteins and the cell cycle of human lung adenocarcinoma (A549) cells. The cellular distribution of zinc and soluble proteins was determined in the whole cell as well as in the cytoplasmic and nuclear fractions. Exogenous zinc in the tested exposure range (0–100 µM) resulted in an altered cellular distribution of both zinc and the soluble proteins, together with total glutathione (GSx), the ratio of glutathione (GSH) to glutathione disulfide (GSSG) and non-protein sulphydryl (NPSH). Surprisingly, a turning point was observed in the re-distribution trend at a concentration of approximately 50 µM ZnSO₄. It is concluded that there exists a regulatory system in A549 cells that maintains the cellular zinc content stable in the presence of a certain range of extracellular zinc concentration. In addition, an MTT assay and flow cytometric analysis showed that the ZnSO₄ treatment led to a bi-phasic variation in viability and a slight fluctuation in the apoptosis of A549 cells. Our results will help to further elucidate zinc-related cell biology and biochemistry.