title: Copper chaperone for Cu/Zn superoxide dismutase is a sensitive biomarker of mild copper deficiency induced by moderately high intakes of zinc.
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).
  
  
  CONCLUSIONS
  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.affiliation: 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.ca
authors.forename: Monica
authors.initials: M
authors.lastname: Iskandar
authors.forename: Eleonora
authors.initials: E
authors.lastname: Swist
authors.forename: Keith D
authors.initials: KD
authors.lastname: Trick
authors.forename: Bingtuan
authors.initials: B
authors.lastname: Wang
authors.forename: Mary R
authors.initials: MR
authors.lastname: L'Abbé
authors.forename: Jesse
authors.initials: J
authors.lastname: Bertinato
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis* / Q000097:blood; D002570:Ceruloplasmin / Q000032:analysis; D003300:Copper / Q000032:analysis / Q000097:blood / Q000172:deficiency*; D004032:Diet; D004912:Erythrocytes / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008297:Male; D018832:Molecular Chaperones / Q000032:analysis* / Q000097:blood; D009752:Nutritional Status; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000008:administration & dosage*
chemical_list: D015415:Biomarkers; C491961:Ccs protein, rat; D018832:Molecular Chaperones; D003300:Copper; D002570:Ceruloplasmin; D015032:Zinc