Phosphorylation of Nuclear Proteins of Peripheral Blood T Lymphocytes Activated by Nickel Sulfate and Mercuric Chloride

Abstract

The phosphorylation of nuclear proteins of peripheral blood T lymphocytes activated by nickel sulfate or mercuric chloride, and from nickel-allergic subjects, was studied in polyacrylamide gel separations of ³²P-labeled proteins. With a preincubation period of the metal salts for 48 h, a marked increase of ³²P label into nonhistone proteins, especially the 30- to 40-kilodalton region, was found compared to the control cultures. This increase was most pronounced in mercuric-chloride-treated cultures, which also showed an increase in labeling of histone H4. The increase in nuclear protein phosphorylation probably reflects an activation of the lymphocytes. Moreover, the difference in phosphorylation pattern between mercuric-chloride- and nickel-sulfate-activated lymphocytes might be due to different mechanisms of action for polyclonal and monoclonal activators, respectively.

Binding of Mercuric Chloride to Nuclear Proteins in Human Peripheral Blood T Lymphocytes

“…We have previously, by electrophoresis and auto radiography, described nuclear phosphoproteins whose phosphorylation could be stimulated by mer curic chloride [6], None of those proteins seem to be identical with the proteins which in this investigation were found to bind high amounts of labelled mercuric chloride. However, a binding of mercuric chloride to non-histone proteins in a similar molecular weight range (30-60 kD) could indicate an activation of nu clear protein kinases, giving an enhanced protein phosphorylation, in turn contributing to the stimu lated DNA synthesis seen in the presence of mer cury.…”

Comprehensive medical examination of a group of patients with alleged adverse effects from dental amalgams

“…From animal studies it is known that the administration of mercury chloride can cause immunologic activation, such as antinuclear antibodies, antibodies against glomerular basement membranes, immune complexes, and activation of the coagulation system (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Eight of the patients in the present study had preexperimentally impaired values in one or more of such immune variables, indicating an altered immunologic activity.…”

“…Contact allergic reactions to dental amalgam are found in a minority of the population (%lo), but there are several reports in animal and in vitro studies on the effects of mercury on the immune system. Thus, mercury chloride may cause non-specific immu-nosuppression (11,12) and proliferation of T and B cells (13), which may induce formation of polyclonal activation of the B lymphocytes, requiring T cells (14)(15)(16). Mercury salts may also induce antinuclear antibodies (14)(15)(16)(17)(18)(19), anti-glomerular basement membrane antibodies, and anti-DNA antibodies (16,(20)(21)(22), increases of serum IgE (15,16,23) and immune complexes (16,(20)(21)(22), and activation of the coagulation system (24).…”

“…Thus, mercury chloride may cause non-specific immu-nosuppression (11,12) and proliferation of T and B cells (13), which may induce formation of polyclonal activation of the B lymphocytes, requiring T cells (14)(15)(16). Mercury salts may also induce antinuclear antibodies (14)(15)(16)(17)(18)(19), anti-glomerular basement membrane antibodies, and anti-DNA antibodies (16,(20)(21)(22), increases of serum IgE (15,16,23) and immune complexes (16,(20)(21)(22), and activation of the coagulation system (24). As an expression of immunoactivation, antibody-mediated renal injury, such as autoimmune glomerulonephritis, may occur (15,17,19,20,22,25).…”

Modulating Effects of Heparin Preparations on the DNA Synthesis Response of Human Peripheral Blood T Lymphocytes Activated by Mercuric Chloride and Nickel Sulfate

“…In an earlier investigation, using human thymocytes [14], heparin in a concentration of 1.1 mg/ml had a stimulating ef fect and the heparin fragment at the same concentra tion was without effect on cell proliferation. Mercuric chloride and nickel sulfate when taken up into lym phocyte nuclei also seem to stimulate the phosphory lation of nuclear proteins [5], the control of which is considered to be important in the regulation of cell proliferation [4], Heparin, on the other hand, has been reported to inhibit phosphorylation of nuclear pro teins [4], Besides an influence on metal effects on the nuclear protein phosphorylation, the heparin prepa rations may also influence the cellular uptake of the metal salts. In this investigation an inhibiting effect was found at 1 h after metal salt addition, but not af ter 72 h, indicating an influence on the early uptake of the metal salts into the cells.…”