Skip Navigation


ToxSci Advance Access originally published online on July 17, 2009
Toxicological Sciences 2009 111(2):345-354; doi:10.1093/toxsci/kfp161
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
111/2/345    most recent
kfp161v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Jiang, G. C.-T.
Right arrow Articles by Aschner, M.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jiang, G. C.-T.
Right arrow Articles by Aschner, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Caenorhabditis elegans Metallothioneins Protect against Toxicity Induced by Depleted Uranium

George C.-T. Jiang*, Sam Hughes{dagger}, Stephen R. Stürzenbaum{dagger}, Lars Evje{ddagger}, Tore Syversen{ddagger} and Michael Aschner*,§,1

* Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232 {dagger} Pharmaceutical Sciences Division, School of Biomedical & Health Sciences, King’s College London, London, UK {ddagger} Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway § Kennedy Center for Research on Human Development, Vanderbilt University Medical Center, Nashville, Tennessee 37232

1 To whom correspondence should be addressed. Fax: 615-936-4080. E-mail: michael.aschner{at}vanderbilt.edu.

Received May 5, 2009; accepted July 13, 2009


  Abstract

Depleted uranium (DU) is a dense and heavy metal used in armor, ammunition, radiation shielding, and counterbalances. The military usage has led to growing public concern regarding the health effects of DU. In this study, we used the nematode, Caenorhabditis elegans, to evaluate the toxicity of DU and its effects in knockout strains of metallothioneins (MTs), which are small thiol-rich proteins that have numerous functions, such as metal sequestration, transport, and detoxification. We examined nematode viability, the accumulation of uranium, changes in MT gene expression by quantitative reverse transcription-PCR, and the induction of green fluorescent protein under the control of the MT promoters, following exposure to DU. Our results indicate that (1) DU causes toxicity in a dose-dependent manner; (2) MTs are protective against DU exposure; and (3) nematode death by DU is not solely a reflection of intracellular uranium concentration. (4) Furthermore, only one of the isoforms of MTs, metallothionein-1 (mtl-1), appears to be important for uranium accumulation in C. elegans. These findings suggest that these highly homologous proteins may have subtle functional differences and indicate that MTs mediate the response to DU.

Key Words: C. elegans; depleted uranium; neurotoxicity; metallothionein; GFP; knockout; TaqMan.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.