Effects of Mercury on Ras/MAP Kinase Signaling in T Cells
Felczak, Aimee M.
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A major task of the immune system is to distinguish self from non-self. Usually the self-reacting cells die by apoptosis before they mature, however, failure of this process results in autoimmune abnormalities. The molecular cause of autoimmunity is unknown. It is proposed that genetic predisposition and environmental toxins both increase susceptibility toward autoimmune diseases. Studies indicate that mercury is a causal agent in autoimmune diseases. In lymphocytes, mercury is suggested to interfere with the apoptotic cell death signaling pathway. Studies demonstrate that mercury induces protein tyrosine phosphorylation, which may be linked to the initiation of intracellular phosphorylation cascades. We hypothesize that mercury interferes with the functioning of the Ras/MAP kinase cell survival pathway, a well-known phosphorylation cascade. To test our hypothesis we performed cell culture experiments evaluating the level of protein activation induced by cell surface receptor stimulating reagents in the presence and absence of mercury. The results from our study indicate that low concentrations (<10 µM) of mercury weakly activate Ras by receptor stimulation. However, mercury had no effect on MAP kinase, a downstream protein of Ras. Thus, inorganic mercury interferes with the completion of Ras/MAP kinase survival pathway, which may play a role in the disregulation of other cell signaling cascades.