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Decreased Erythrocyte CCS Content is a Biomarker of Copper Overload in Rats
Nutrition Research Division, Health Products and Food Branch, Health Canada, Sir Frederick G. Banting Research Centre, 251 Sir Frederick Banting Driveway, Ottawa, Ontario, Canada
* Author to whom correspondence should be addressed.
Received: 26 May 2010; in revised form: 25 June 2010 / Accepted: 30 June 2010 / Published: 2 July 2010
(This article belongs to the Special Issue Biomarkers
Abstract: Copper (Cu)is an essential trace metal that is toxic in excess. It is therefore important to be able to accurately assess Cu deficiency or overload. Cu chaperone for Cu/Zn superoxide dismutase (CCS) protein expression is elevated in tissues of Cu-deficient animals. Increased CCS content in erythrocytes is particularly sensitive to decreased Cu status. Given the lack of a non-invasive, sensitive and specific biomarker for the assessment of Cu excess, we investigated whether CCS expression in erythrocytes reflects Cu overload. Rats were fed diets containing normal or high levels of Cu for 13 weeks. Diets contained 6.3 ± 0.6 (Cu-N), 985 ± 14 (Cu-1000) or 1944 ± 19 (Cu-2000) mg Cu/kg diet. Rats showed a variable response to the high Cu diets. Some rats showed severe Cu toxicity, while other rats showed no visible signs of toxicity and grew normally. Also, some rats had high levels of Cu in liver, whereas others had liver Cu concentrations within the normal range. Erythrocyte CCS protein expression was 30% lower in Cu-2000 rats compared to Cu-N rats (P < 0.05). Notably, only rats that accumulated high levels of Cu in liver had lower erythrocyte CCS (47% reduction, P < 0.05) compared to rats fed normal levels of Cu. Together, these data indicate that decreased erythrocyte CCS content is associated with Cu overload in rats and should be evaluated further as a potential biomarker for assessing Cu excess in humans.
Keywords: copper overload; CCS; biomarker; rat; erythrocytes
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Bertinato, J.; Sherrard, L.; Plouffe, L.J. Decreased Erythrocyte CCS Content is a Biomarker of Copper Overload in Rats. Int. J. Mol. Sci. 2010, 11, 2624-2635.
Bertinato J, Sherrard L, Plouffe LJ. Decreased Erythrocyte CCS Content is a Biomarker of Copper Overload in Rats. International Journal of Molecular Sciences. 2010; 11(7):2624-2635.
Bertinato, Jesse; Sherrard, Lindsey; Plouffe, Louise J. 2010. "Decreased Erythrocyte CCS Content is a Biomarker of Copper Overload in Rats." Int. J. Mol. Sci. 11, no. 7: 2624-2635.