The role of MAPK in the biphasic dose-response phenomenon induced by cadmium and mercury in HEK293 cells

Some studies show that Cd2+ and Hg2+ may induce cell proliferation and apoptosis via biphasic dose-response relationship in human cells. However, mechanisms underlying this phenomenon are still in puzzle. In this study, we aim at detecting the biphasic effects of Cd2+ and Hg2+ on proliferation and apoptosis of human embryonic kidney 293 (HEK293) cells, analyzing the change of the mitogen-activated protein kinase (MAPK) pathways, and discussing the relationship between them. The results demonstrate that Cd2+ and Hg2+ can stimulate cell proliferation at lower concentrations (0.05 and 0.5 mu M) but inhibit it at higher concentrations (50 and 500 mu M). Apoptosis increases at higher concentrations (50 and 500 mu M) of Cd2+ and Hg2+. While 0.5 mu M Cd2+ and Hg2+ decrease the JNK phosphorylation, 50 mu M Cd2+ and Hg2+ increase the JNK and P38 phosphorylation. When HEK293 cells are treated with 20 mu M JNK inhibitor or 100 mu M ERK1/2 inhibitor, the cell proliferation do not increase significantly at low concentrations (0.05 and 0.5 mu M), but still decrease at high concentrations (50 and 500 mu M). When HEK293 cells are treated with 20 mu M P38 inhibitor, the tendency of cell proliferation is not affected. Data in our study suggests that activation of MAPK pathway may be involved in the biphasic effect induced by Cd2+ and Hg2+. (C) 2009 Elsevier Ltd. All rights reserved.