title: Inorganic mercury attenuates CD95-mediated apoptosis by interfering with formation of the death inducing signaling complex.
abstract: Inorganic mercury (Hg2+) modulates several lymphocyte signaling pathways and has been implicated as an environmental factor linked to autoimmune disease. From the standpoint that autoimmune diseases represent disorders of cell accumulation, in which dysregulated apoptosis may be one mechanism leading to the accumulation of autoreactive lymphocytes, we have been investigating the influences of Hg2+ on CD95-mediated apoptosis. We demonstrate here that low and noncytotoxic concentrations of Hg2+ impair CD95 agonist-induced apoptosis in representative Type-I and Type-II T cell lines. Hg2+ treatment blocks the CD95 agonist-induced activation of initiator and effector caspases as well as the association between CD95 and the signaling adaptor, FADD. CD95 multimerization does not appear to be affected by Hg2+. Thus, the Hg2+ sensitive step within the CD95 death pathway is localized to the level of the death inducing signaling complex (DISC). Disruption of proper DISC formation may be a biochemical mechanism whereby Hg2+ contributes to autoimmune disease.
authors.affiliation: Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. michael_mccabe@urmc.rochester.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McCabe
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Whitekus
authors.forename: Joogyung
authors.initials: J
authors.lastname: Hyun
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Eckles
authors.forename: Geniece
authors.initials: G
authors.lastname: McCollum
authors.forename: Allen J
authors.initials: AJ
authors.lastname: Rosenspire
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019169:Jurkat Cells; D008628:Mercury / Q000494:pharmacology*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D019014:fas Receptor / Q000276:immunology*
chemical_list: D019014:fas Receptor; D008628:Mercury