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Gene Review

CP  -  ceruloplasmin (ferroxidase)

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Disease relevance of CP

  • Glutathione may thus function to shuttle the metal from the membrane copper pump, as the Wilson disease ATPase, and ceruloplasmin in the secretory compartments of the cell [1].
  • All the treatments increased whole blood copper levels and plasma caeruloplasmin (ferroxidase) activity in ewes, and protected their lambs from swayback [2].
  • The concentrations of plasma ceruloplasmin, plasma fibrinogen, serum haptoglobin and the major cell types in blood together with liveweight changes were monitored during the acute phase response in sheep [3].
  • The levels of C-reactive protein (CRP), haptoglobin, ceruloplasmin, fibrinogen, zinc, iron and calcium, which are the indicators of immune function and infectious diseases were analysed [4].

High impact information on CP

  • The data presented here indicate a direct relationship between the extent of inhibition of agonist-triggered endothelial nitric oxide synthase activation and CP-induced enrichment of the copper content of endothelial cells [5].
  • The subcellular distribution of the metal seems to be of relevance to the inhibitory effect of CP, because it was mimicked by copper chelates, like copper-histidine, able to selectively enrich the cytosolic fraction of cells, but not by copper salts, which preferentially located the metal to the particulate fraction [5].
  • The reactivity with dioxygen of a mammalian (sheep) ceruloplasmin, anaerobically reduced with ascorbate, was found to depend on the state of the Type 2 and Type 3 copper centers, as monitored by EPR and optical spectroscopy [6].
  • Overall, the structure and expression of sCP appeared similar to other mammals, suggesting that abnormalities in CP were not responsible for the unusual sheep copper phenotype [7].
  • Northern blot analysis of sheep tissue revealed that the sheep ceruloplasmin gene (sCP) was expressed primarily in the liver, but low levels of mRNA were detected in the hypothalamus, spleen and uterus [7].

Biological context of CP

  • Ceruloplasmin activity, total plasma copper and hematocrit were lower in zinc-supplemented sheep [8].
  • Peripheral plasma or serum concentrations of haptoglobin, seromucoid, ceruloplasmin and 15-keto-13,14-dihydro-prostaglandin F2 alpha (PGFM) were measured up to six weeks postpartum [9].
  • The data presented in this paper constitute the first evidence of impairment of the endothelium-dependent vasodilatation by a plasma protein and may shed some light on the still uncertain physiological role of ceruloplasmin [10].
  • At the dose level given serum inorganic phosphorus was not significantly increased and packed cell volume, serum proteins and ceruloplasmin concentrations remained constant [11].

Anatomical context of CP


Associations of CP with chemical compounds

  • Dietary CP and digestible protein (DP) were closely related (DP = .879[CP%] -3.66; r2 = .91), indicating that for urea, CM and BC total tract N digestibility was not influenced by theoretical ruminal degradability [14].
  • Trichloroacetic acid soluble Cu, ceruloplasmin and superoxide dismutase activities in the plasma of ewes were decreased (P less than .05) by TTM [15].
  • 1. The effect of acute duodenal infusion of 99Mo-labelled sodium tetrathiomolybdate on caeruloplasmin (ferroxidase; EC was examined in sheep [16].
  • Changes in blood ceruloplasmin and SGOT levels and in the comparative rate of accumulation of liver copper indicated that the addition of ammonium molybdate to the concentrate diet might be a useful method of reducing the risk of nutritional copper poisoning in housed sheep [17].
  • However, oestradiol-treated ewes had lower plasma concentrations of 15-keto-13,14-dihydro-prostaglandin F2alpha (P<0.01), alpha1-acid glycoprotein (P<0.05) and ceruloplasmin (P<0.001); but, not haptoglobin [18].

Analytical, diagnostic and therapeutic context of CP


  1. Reconstitution of ceruloplasmin by the Cu(I)-glutathione complex. Evidence for a role of Mg2+ and ATP. Musci, G., Di Marco, S., Bellenchi, G.C., Calabrese, L. J. Biol. Chem. (1996) [Pubmed]
  2. Copper heptonate for the treatment of hypocupraemia in sheep. McPhee, I.M., Cawley, G.D. Vet. Rec. (1988) [Pubmed]
  3. Acute phase response of sheep: changes in the concentrations of ceruloplasmin, fibrinogen, haptoglobin and the major blood cell types associated with pulmonary damage. Pfeffer, A., Rogers, K.M. Res. Vet. Sci. (1989) [Pubmed]
  4. Effect of Mannheimia (Pasteurella) haemolytica infection on acute-phase proteins and some mineral levels in colostrum-breast milk-fed or colostrum-breast milk-deprived sheep. Ulutas, P.A., Ozpinar, A. Vet. Res. Commun. (2006) [Pubmed]
  5. Inhibition of endothelial nitric-oxide synthase by ceruloplasmin. Bianchini, A., Musci, G., Calabrese, L. J. Biol. Chem. (1999) [Pubmed]
  6. Presence of coupled trinuclear copper cluster in mammalian ceruloplasmin is essential for efficient electron transfer to oxygen. Calabrese, L., Carbonaro, M., Musci, G. J. Biol. Chem. (1989) [Pubmed]
  7. Cloning and expression analysis of the sheep ceruloplasmin cDNA. Lockhart, P.J., Mercer, J.F. Gene (1999) [Pubmed]
  8. Intracellular distribution of copper and zinc in sheep: effect of age and dietary levels of the metals. Saylor, W.W., Leach, R.M. J. Nutr. (1980) [Pubmed]
  9. Acute phase protein response of ewes and the release of PGFM in relation to uterine involution and the presence of intrauterine bacteria. Regassa, F., Noakes, D.E. Vet. Rec. (1999) [Pubmed]
  10. Ceruloplasmin impairs endothelium-dependent relaxation of rabbit aorta. Cappelli-Bigazzi, M., Ambrosio, G., Musci, G., Battaglia, C., Bonaccorsi di Patti, M.C., Golino, P., Ragni, M., Chiariello, M., Calabrese, L. Am. J. Physiol. (1997) [Pubmed]
  11. Serum calcium fractions in sheep treated with Solanum malacoxylon. Bingley, J.B., Ruksan, B.E., Carrillo, B.J. Res. Vet. Sci. (1976) [Pubmed]
  12. The interaction of ceruloplasmin with Kupffer cells. Dini, L., Carbonaro, M., Musci, G., Calabrese, L. Eur. J. Cell Biol. (1990) [Pubmed]
  13. Influence of triiodothyronine injections on calf immune response to an infectious bovine rhinotracheitis virus challenge and nitrogen balance of lambs. Cole, N.A., Gallavan, R.H., Rodriguez, S.L., Purdy, C.W. J. Anim. Sci. (1994) [Pubmed]
  14. Effects of ruminal escape proteins and canola meal on nitrogen utilization by growing lambs. Matras, J., Bartle, S.J., Preston, R.L. J. Anim. Sci. (1990) [Pubmed]
  15. The effects of ammonium tetrathiomolybdate intake on tissue copper and molybdenum in pregnant ewes and lambs. Kincaid, R.L., White, C.L. J. Anim. Sci. (1988) [Pubmed]
  16. The fate of 99Mo-labelled sodium tetrathiomolybdate after duodenal administration in sheep: the effect on caeruloplasmin (EC diamine oxidase activity and plasma copper. Mason, J., Lamand, M., Kelleher, C.A. Br. J. Nutr. (1980) [Pubmed]
  17. The use of molybdenum for the prevention of nutritional copper poisoning in housed sheep. Harker, D.B. Vet. Rec. (1976) [Pubmed]
  18. The effect of oestradiol on postpartum uterine involution in sheep. Sheldon, I.M., Noakes, D.E., Bayliss, M., Dobson, H. Anim. Reprod. Sci. (2003) [Pubmed]
  19. Divalent cation binding to ceruloplasmin. Musci, G., Bonaccorsi di Patti, M.C., Petruzzelli, R., Giartosio, A., Calabrese, L. Biometals (1996) [Pubmed]
  20. Serum and plasma ceruloplasmin in humans. Louro, M.O., Tutor, J.C., Paz, J.M. J. Clin. Chem. Clin. Biochem. (1989) [Pubmed]
  21. Acute phase protein response, food intake, liveweight change and lesions following intrathoracic injection of yeast in sheep. Pfeffer, A., Rogers, K.M., O'Keeffe, L., Osborn, P.J. Res. Vet. Sci. (1993) [Pubmed]
  22. Influence of sex hormones on the subcellular distribution of copper in sheep liver. Russanov, E., Banskalieva, V., Ljutakova, S. Res. Vet. Sci. (1981) [Pubmed]
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