Document Detail

Low concentrations of inorganic mercury inhibit Ras activation during T cell receptor-mediated signal transduction.
MedLine Citation:
PMID:  11714248     Owner:  NLM     Status:  MEDLINE    
Mercury is widespread in the environment and consequently there are large populations that are currently exposed to low levels of mercury as a result of ubiquitous environmental factors. Whether these environmental levels of mercury are harmful is a matter of current debate, with epidemiological and animal studies suggesting detrimental effects on the immune and nervous systems. However, specific cellular effects of low concentrations of mercury have been hard to characterize. We now demonstrate that subtoxic concentrations of HgCl(2) can potently (maximal at 1 microM) increase Ras.GTP levels in Jurkat, a human T cell line. Remarkably, this activation of Ras occurs without a concomitant increase in MAP kinase activation, suggesting that mercury may direct Ras into a nonproductive state. In addition to its direct effect on Ras, concentrations of HgCl(2) as low as 0.6 microM inhibited the ability of the T cell receptor to activate Ras and MAP kinase. The inhibitory effect of mercury is selective, as activation of MAP kinase by phorbol diesters remain intact. Since the Ras/MAP kinase pathway is both highly conserved and central to signal transduction processes mediated by a myriad of diverse membrane receptor systems in a variety of cell types, these results suggest a mechanism for adverse health effects resulting from exposure to low levels of mercury. They also support a model for regulation of the Ras/MAP kinase pathway, whereby partial but unproductive activation of Ras can diminish signaling from cell surface receptors.
R R Mattingly; A Felczak; C C Chen; M J McCabe; A J Rosenspire
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  176     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-20     Completed Date:  2001-12-07     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  162-8     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Academic Press.
Department of Pharmacology, Wayne State University, Detroit, Michigan 48201, USA.
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MeSH Terms
Antibodies, Monoclonal / pharmacology
Antigens, CD3 / immunology
Enzyme Activation / drug effects
Guanosine Triphosphate / metabolism
Jurkat Cells
Mercury / pharmacology*
Mitogen-Activated Protein Kinases / metabolism
Receptors, Antigen, T-Cell / physiology*
Signal Transduction*
Tetradecanoylphorbol Acetate / pharmacology
ras Proteins / metabolism*
Grant Support
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD3; 0/Receptors, Antigen, T-Cell; 16561-29-8/Tetradecanoylphorbol Acetate; 7439-97-6/Mercury; 86-01-1/Guanosine Triphosphate; EC Protein Kinases; EC Proteins

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