Inorganic mercury dissociates preassembled Fas/CD95 receptor oligomers in T lymphocytes.
Genetically susceptible rodents exposed to low burdens of inorganic mercury (Hg2+) develop autoimmune disease. Previous studies have shown that low, noncytotoxic levels of Hg2+ inhibit Fas-mediated apoptosis in T cells. These results suggest that inhibition of the Fas death receptor pathway potentially contributes to autoimmune disease after Hg2+ exposure, as a consequence of disruption of peripheral tolerance. The formation of active death inducing signaling complexes (DISC) following CD95/Fas receptor oligomerization is a primary step in the Fas-mediated apoptotic pathway. Other recent studies have shown that Hg2+ at concentrations that inhibit apoptosis also inhibit formation of active DISC, suggesting that inhibition of DISC is the mechanism responsible for Hg2+-mediated inhibition of apotosis. Preassociated Fas receptors have been implicated as key elements necessary for the production of functional DISC. We present evidence in this study showing that low and nontoxic concentrations of Hg2+ induce the dissociation of preassembled Fas receptor complexes in Jurkat T cells. Thus, this Hg2+-induced event should subsequently decrease the amount of preassembled Fas available for DISC formation, potentially resulting in the attenuation of Fas-mediated apoptosis in T lymphocytes.
Ziemba
Stamatina E
SE
Department of Biological Sciences, Wayne State University, 5047 Gullen Mall, Detroit, MI 48202, USA.
McCabe
Michael J
MJ
Rosenspire
Allen J
AJ
D001704:Biopolymers; D015153:Blotting, Western; D002712:Chlorides / Q000494:pharmacology; D053418:Death Domain Receptor Signaling Adaptor Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D019169:Jurkat Cells; D008627:Mercuric Chloride / Q000633:toxicity*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D017967:Zinc Compounds / Q000494:pharmacology; D019014:fas Receptor / Q000378:metabolism*
D001704:Biopolymers; D002712:Chlorides; D053418:Death Domain Receptor Signaling Adaptor Proteins; D004785:Environmental Pollutants; D018124:Receptors, Tumor Necrosis Factor; D017967:Zinc Compounds; D019014:fas Receptor; D008627:Mercuric Chloride; C016837:zinc chloride