Inorganic mercury dissociates preassembled Fas/CD95 receptor oligomers in T lymphocytes
- Department of Biological Sciences, Wayne State University, 5047 Gullen Mall, Detroit, MI 48202 (United States)
- Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 (United States)
Genetically susceptible rodents exposed to low burdens of inorganic mercury (Hg{sup 2+}) develop autoimmune disease. Previous studies have shown that low, noncytotoxic levels of Hg{sup 2+} inhibit Fas-mediated apoptosis in T cells. These results suggest that inhibition of the Fas death receptor pathway potentially contributes to autoimmune disease after Hg{sup 2+} 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 Hg{sup 2+} at concentrations that inhibit apoptosis also inhibit formation of active DISC, suggesting that inhibition of DISC is the mechanism responsible for Hg{sup 2+}-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 Hg{sup 2+} induce the dissociation of preassembled Fas receptor complexes in Jurkat T cells. Thus, this Hg{sup 2+}-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.
- OSTI ID:
- 20721863
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 206, Issue 3; Other Information: DOI: 10.1016/j.taap.2004.11.014; PII: S0041-008X(04)00520-4; Copyright (c) 2004 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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