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Calafato, S, Swain, S, Hughes, S, Kille, P and Stürzenbaum, SR (2008) Knock down of Caenorhabditis elegans cutc-1 exacerbates the sensitivity toward high levels of copper. Toxicol. Sci. 106:384-91
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 CuSO(4) 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.
Amino Acid Sequence; Animals; Base Sequence; Caenorhabditis elegans/drug effects; Caenorhabditis elegans/genetics; Caenorhabditis elegans Proteins/chemistry; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/physiology; Copper Sulfate/metabolism; Copper Sulfate/toxicity; DNA Primers; Gene Knockdown Techniques; Gene Silencing; Humans; Molecular Sequence Data; Polymerase Chain Reaction; RNA Interference; Sequence Homology, Amino Acid