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Copper chaperone for Cu/Zn superoxide dismutase is a sensitive biomarker of mild copper deficiency induced by moderately high intakes of zinc.
Nutr J 2005; 4:35NJ

Abstract

BACKGROUND

Small increases in zinc (Zn) consumption above recommended amounts have been shown to reduce copper (Cu) status in experimental animals and humans. Recently, we have reported that copper chaperone for Cu/Zn superoxide dismutase (CCS) protein level is increased in tissues of overtly Cu-deficient rats and proposed CCS as a novel biomarker of Cu status.

METHODS

Weanling male Wistar rats were fed one of four diets normal in Cu and containing normal (30 mg Zn/kg diet) or moderately high (60, 120 or 240 mg Zn/kg diet) amounts of Zn for 5 weeks. To begin to examine the clinical relevance of CCS, we compared the sensitivity of CCS to mild Cu deficiency, induced by moderately high intakes of Zn, with conventional indices of Cu status.

RESULTS

Liver and erythrocyte CCS expression was significantly (P < 0.05) increased in rats fed the Zn-60 and/or Zn-120 diet compared to rats fed normal levels of Zn (Zn-30). Erythrocyte CCS expression was the most sensitive measure of reduced Cu status and was able to detect a decrease in Cu nutriture in rats fed only twice the recommended amount of Zn. Liver, erythrocyte and white blood cell CCS expression showed a significant (P < 0.05) inverse correlation with plasma and liver Cu concentrations and caeruloplasmin activity. Unexpectedly, rats fed the highest level of Zn (Zn-240) showed overall better Cu status than rats fed a lower level of elevated Zn (Zn-120). Improved Cu status in these rats correlated with increased duodenal mRNA expression of several Zn-trafficking proteins (i.e. MT-1, ZnT-1, ZnT-2 and ZnT-4).

CONCLUSION

Collectively, these data show that CCS is a sensitive measure of Zn-induced mild Cu deficiency and demonstrate a dose-dependent biphasic response for reduced Cu status by moderately high intakes of Zn.

Authors+Show Affiliations

Nutrition Research Division, Food Directorate, Health Products and Food Branch, Health Canada, 2203C Banting Research Centre, Ottawa, ON, K1A 0L2, Canada. monica.iskandar@hc-sc.gc.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16307684

Citation

Iskandar, Monica, et al. "Copper Chaperone for Cu/Zn Superoxide Dismutase Is a Sensitive Biomarker of Mild Copper Deficiency Induced By Moderately High Intakes of Zinc." Nutrition Journal, vol. 4, 2005, p. 35.
Iskandar M, Swist E, Trick KD, et al. Copper chaperone for Cu/Zn superoxide dismutase is a sensitive biomarker of mild copper deficiency induced by moderately high intakes of zinc. Nutr J. 2005;4:35.
Iskandar, M., Swist, E., Trick, K. D., Wang, B., L'Abbé, M. R., & Bertinato, J. (2005). Copper chaperone for Cu/Zn superoxide dismutase is a sensitive biomarker of mild copper deficiency induced by moderately high intakes of zinc. Nutrition Journal, 4, p. 35.
Iskandar M, et al. Copper Chaperone for Cu/Zn Superoxide Dismutase Is a Sensitive Biomarker of Mild Copper Deficiency Induced By Moderately High Intakes of Zinc. Nutr J. 2005 Nov 24;4:35. PubMed PMID: 16307684.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Copper chaperone for Cu/Zn superoxide dismutase is a sensitive biomarker of mild copper deficiency induced by moderately high intakes of zinc. AU - Iskandar,Monica, AU - Swist,Eleonora, AU - Trick,Keith D, AU - Wang,Bingtuan, AU - L'Abbé,Mary R, AU - Bertinato,Jesse, Y1 - 2005/11/24/ PY - 2005/09/23/received PY - 2005/11/24/accepted PY - 2005/11/26/pubmed PY - 2006/4/25/medline PY - 2005/11/26/entrez SP - 35 EP - 35 JF - Nutrition journal JO - Nutr J VL - 4 N2 - BACKGROUND: Small increases in zinc (Zn) consumption above recommended amounts have been shown to reduce copper (Cu) status in experimental animals and humans. Recently, we have reported that copper chaperone for Cu/Zn superoxide dismutase (CCS) protein level is increased in tissues of overtly Cu-deficient rats and proposed CCS as a novel biomarker of Cu status. METHODS: Weanling male Wistar rats were fed one of four diets normal in Cu and containing normal (30 mg Zn/kg diet) or moderately high (60, 120 or 240 mg Zn/kg diet) amounts of Zn for 5 weeks. To begin to examine the clinical relevance of CCS, we compared the sensitivity of CCS to mild Cu deficiency, induced by moderately high intakes of Zn, with conventional indices of Cu status. RESULTS: Liver and erythrocyte CCS expression was significantly (P < 0.05) increased in rats fed the Zn-60 and/or Zn-120 diet compared to rats fed normal levels of Zn (Zn-30). Erythrocyte CCS expression was the most sensitive measure of reduced Cu status and was able to detect a decrease in Cu nutriture in rats fed only twice the recommended amount of Zn. Liver, erythrocyte and white blood cell CCS expression showed a significant (P < 0.05) inverse correlation with plasma and liver Cu concentrations and caeruloplasmin activity. Unexpectedly, rats fed the highest level of Zn (Zn-240) showed overall better Cu status than rats fed a lower level of elevated Zn (Zn-120). Improved Cu status in these rats correlated with increased duodenal mRNA expression of several Zn-trafficking proteins (i.e. MT-1, ZnT-1, ZnT-2 and ZnT-4). CONCLUSION: Collectively, these data show that CCS is a sensitive measure of Zn-induced mild Cu deficiency and demonstrate a dose-dependent biphasic response for reduced Cu status by moderately high intakes of Zn. SN - 1475-2891 UR - https://www.unboundmedicine.com/medline/citation/16307684/Copper_chaperone_for_Cu/Zn_superoxide_dismutase_is_a_sensitive_biomarker_of_mild_copper_deficiency_induced_by_moderately_high_intakes_of_zinc_ L2 - https://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-4-35 DB - PRIME DP - Unbound Medicine ER -