Mercuric chloride induces increases in both cytoplasmic and nuclear free calcium ions through a protein phosphorylation-linked mechanism

Abstract

The mechanism of the lymphocyte stimulatory action of sulfhydryl group-reactive mercuric ions was studied with respect to its potential ability to induce a protein tyrosine phosphorylation-linked signal for mobilization of free Ca 2+ into cytoplasm and nucleus of the cell. Exposure of human leukamic T cell line (Jurkat) cells to high (1 mM) and low (0.01 mM) concentrations of HgCl 2 induced tyrosine phosphorylation of multiple proteins in a concentration-dependent manner. Confocal microscopy directly visualized the time course localization of Ca 2+ inside the cells after exposure to HgCl 2. The onset and level of Ca 2+ mobilization following HgCl 2 exposure were in parallel to those of protein tyrosine phosphorylation. Interestingly, by either concentration of HgCl 2, Ca 2+ was mobilized in both cytoplasm and nucleus almost simultaneously, and the level of Ca 2+ mobilization in the nucleus was more than that in the cytoplasm. All the HgCl 2-mediated Ca 2+ mobilization was prevented by addition of protein kinase inhibitor staurosporin prior to HgCl 2. These results suggest that heavy metal stress triggers a protein tyrosine phosphorylation-linked signal that leads to a nuclear event-dominant Ca 2+ mobilization.