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Author Gill, Randall ♦ Lanni, Lydia ♦ Jen, K. -L. Catherine ♦ McCabe, Michael J. ♦ Rosenspire, Allen
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ APOPTOSIS ♦ CARBOXYLIC ACIDS ♦ CHILDREN ♦ DISEASES ♦ ENVIRONMENTAL EXPOSURE ♦ FOOD ♦ IN VITRO ♦ IN VIVO ♦ LYMPHOCYTES ♦ MERCURY ♦ NERVOUS SYSTEM ♦ WOMEN
Abstract In the United States the principal environmental exposure to mercury is through dietary consumption of sea food. Although the mechanism by which low levels of mercury affect the nervous system is not well established, epidemiological studies suggest that low level exposure of pregnant women to dietary mercury can adversely impact cognitive development in their children, but that Docosahexaenoic acid (DHA), the most prominent n-polyunsaturated fatty acid (n-PUFA) present in fish may counteract negative effects of mercury on the nervous system. Aside from effects on the nervous system, epidemiological and animal studies have also suggested that low level mercury exposure may be a risk factor for autoimmune disease. However unlike the nervous system where a mechanism linking mercury to impaired cognitive development remains elusive, we have previously suggested a potential mechanism linking low level mercury exposures to immune system dysfunction and autoimmunity. In the immune system it is well established that disruption of CD95 mediated apoptosis leads to autoimmune disease. We have previously shown in vitro as well as in vivo that in lymphocytes burdened with low levels of mercury, CD95 mediated cell death is impaired. In this report we now show that DHA counteracts the negative effect of mercury on CD95 signaling in T lymphocytes. T cells which have been pre-exposed to DHA are able to cleave pro-caspase 3 and efficiently signal programmed cell death through the CD95 signaling pathway, whether or not they are burdened with low levels of mercury. Thus DHA may lower the risk of autoimmune disease after low level mercury exposures. - Highlights: • Inorganic mercury (Hg{sup 2+}) interferes with CD95 mediated cell death in Jurkat T cells • DHA restores the ability of CD95 to signal cell death in Hg{sup 2+} intoxicated T cells • The restoration of CD95 mediated cell death by DHA is correlated with increased activation of Caspase 3.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-01-01
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 282
Issue Number 1


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