ToxSci Advance Access published online on August 22, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn180
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Knockdown of Caenorhabditis elegans cutc-1 exacerbates the sensitivity towards high levels of copper
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* University of Cardiff, School of Biosciences, Main Building, Park Place, Cardiff CF10 3TL, United Kingdom
School of Biomedical & Health Sciences, Pharmaceutical Science Division, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom
E-mail addresses: Sara Calafato, calafato{at}cardiff.ac.uk; Suresh Swain, suresh.swain{at}kcl.ac.uk; Samantha Hughes, Samantha.Hughes{at}kcl.ac.uk; Peter Kille, Kille{at}cf.ac.uk; Stephen Sturzenbaum, stephen.sturzenbaum{at}kcl.ac.uk
1 Name and address of corresponding author: Dr. Stephen Stürzenbaum, School of Biomedical & Health Sciences, Pharmaceutical Science Division, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom, Telephone: +44 (0)207 848 4406, Fax: +44 (0)207 848 4500, Email: stephen.sturzenbaum{at}kcl.ac.uk
Received July 2, 2008; revision received August 14, 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 whilst 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 lifespan. 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 was analysed. Using qPCR technology, cutc-1 was found to be down regulated with increasing CuSO4 concentrations. However, although total (whole body) copper levels increased in nematodes exposed to elevated levels of copper, wild type and knockdown of cutc-1 by RNA-mediated interference (RNAi) were statistically indistinguishable. Nevertheless, RNAi of cutc-1 affected brood size, growth a marked increase in protruding vulva and bagging bag of worm 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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