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-reactive mercuric ions was studied with respect to its potential ability to induce a protein tyrosine phosphorylation-linked signal for mobilization of free 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 concentration-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 parallel 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 was more than that in the cytoplasm. All the HgCl2-mediated Ca2+ mobilization was prevented by addition of protein kinase inhibitor staurosporin prior to HgCl2. These results suggest that heavy metal stress triggers a protein tyrosine phosphorylation-linked signal that leads to a nuclear event-dominant Ca2+ mobilization.
Parashar
A
A
Department of Immunology, Nagoya University School of Medicine, Japan.
Akhand
A A
AA
Rawar
R
R
Furuno
T
T
Nakanishi
M
M
Kato
M
M
Suzuki
H
H
Nakashima
I
I
D020013:Calcium Signaling / Q000187:drug effects*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000633:toxicity*; D018613:Microscopy, Confocal; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011506:Proteins / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005609:Free Radicals; D011506:Proteins; D008627:Mercuric Chloride; D011493:Protein Kinase C; D019311:Staurosporine