ToxSci Advance Access originally published online on August 22, 2008
Toxicological Sciences 2008 106(2):384-391; doi:10.1093/toxsci/kfn180
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Knock down of Caenorhabditis elegans cutc-1 Exacerbates the Sensitivity Toward High Levels of Copper
,*,1
* School of Biosciences, University of Cardiff, Main Building, Park Place, Cardiff CF10 3TL, UK
Pharmaceutical Science Division, School of Biomedical and Health Sciences, King's College London, London SE1 9NH, UK
1 To whom correspondence should be addressed at Pharmaceutical Science Division, School of Biomedical and Health Sciences, King's College London, 150 Stamford Street, London SE1 9NH, UK. Fax: +44 207 848 4500. E-mail: stephen.sturzenbaum{at}kcl.ac.uk.
Received July 2, 2008; accepted August 14, 2008
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Abstract |
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Copper, though toxic in excess, is an essential trace element that serves as a cofactor in many critical biological processes such as respiration, iron transport, and oxidative stress protection. To maintain this balance between requirement and toxicity, biological systems have developed intricate systems allowing the preservation of homeostasis while ensuring delivery of copper to the appropriate cellular component. The nematode Caenorhabditis elegans was exploited to assess the effects of copper toxicity at the population level to identify key changes in life cycle traits including, lethality, brood size, generation time, growth, and life span. To enhance our understanding of the complexities of copper homeostasis at the genetic level, the expression profile and functional significance of a putative copper cytoplasmic metallochaperone cutc-1 were analyzed. Using quantitative PCR technology, cutc-1 was found to be downregulated with increasing CuSO4 concentrations. However, although total (whole body) copper levels increased in nematodes exposed to elevated levels of copper, wild-type and knock down of cutc-1 by RNA-mediated interference (RNAi) were statistically indistinguishable. Nevertheless, RNAi of cutc-1 affected brood size, growth and induced a marked increase in protruding vulva and bagging phenotypes at higher copper exposures. This indicates that cutc-1 plays a crucial role in the protection from excess copper.
Key Words: copper; C. elegans; cutC; cutc-1.
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