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

The mechanism of the lymphocyte stimulatory action of sulfhydryl group-reac tive mercuric ions was studied with respect to its potential ability to ind uce a protein tyrosine phosphorylation-linked signal for mobilization of fr ee Ca2+ 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 HgCl2, induced tyrosine phosphorylation of multiple proteins in a concen tration-dependent manner. Confocal microscopy directly visualized the time course localization of Ca2+ inside the cells after exposure to HgCl2,. The onset and level of Ca2+ mobilization following HgCl2, exposure were in para llel to those of protein tyrosine phosphorylation. Interestingly, by either concentration of HgCl2,, Ca2+ was mobilized in both cytoplasm and nucleus almost simultaneously, and the level of Ca2+ mobilization in the nucleus wa s more than that in the cytoplasm. All the HgCl2-mediated Ca2+ mobilization was prevented by addition of protein kinase inhibitor stauros-porin prior to HgCl2,. These results suggest that heavy metal stress triggers a protein tyrosine phosphorylation-linked signal that leads to a nuclear event-domin ant Ca2+ mobilization. (C) 1998 Elsevier Science Inc.