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Gene Review

Cp  -  ceruloplasmin (ferroxidase)

Rattus norvegicus

Synonyms: Ceruloplasmin, Ferroxidase
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Disease relevance of Cp


Psychiatry related information on Cp


High impact information on Cp

  • In indomethacin-treated rabbits, however, ceruloplasmin at the same high doses failed to induce angiogenesis [7].
  • Changes in serum ceruloplasmin levels, bile copper excretion capacity, and liver histology were in concordance with decreases in liver copper levels [8].
  • Wilson's disease is an autosomal recessive disorder of copper metabolism characterized by abnormal copper accumulation in the liver and low serum ceruloplasmin activity [9].
  • These changes are paralleled by a decreased estrogen responsiveness of the liver, as evidenced by the plasma ceruloplasmin level [10].
  • The mode of transport of ceruloplasmin (CP) into the liver was investigated in fractionated liver cell suspensions [11].

Chemical compound and disease context of Cp


Biological context of Cp

  • By using RT-PCR, we demonstrate that FP and CP gene expression is up-regulated by treatment with the pro-inflammatory cytokine IL-1beta in rat C6 cells, taken as a glial cellular model [1].
  • The expression of GPI-Cp on the surface of these cells increases with postnatal development and is regulated in vitro by cell density, time in culture, and various extracellular matrix molecules [17].
  • Using these cDNA clones in RNA blot analysis, a single 3.7-kilobase ceruloplasmin-specific transcript is detected in fetal rat liver and lung by day 15 of gestation [3].
  • The derived amino acid sequence of rat ceruloplasmin is 93% homologous to the corresponding human sequence and contains a 19-amino acid leader peptide plus 1040 amino acids of mature protein [3].
  • cDNA clones corresponding to rat ceruloplasmin were isolated from newborn rat lung and liver cDNA libraries and the nucleotide sequence was obtained [3].

Anatomical context of Cp


Associations of Cp with chemical compounds


Regulatory relationships of Cp


Other interactions of Cp

  • In the AZn rats, IL-1 beta infusion resulted in increased plasma copper (Cu) concentrations and ceruloplasmin (Cp) activity, and decreased iron (Fe) concentrations throughout the 7d period [22].
  • Following stimulation with IL-1beta, a higher expression level of CP and FP was also confirmed by Western blotting [1].
  • Here, we have investigated processing of glypican-1 in rat C6 glioma cells and the possible participation of the copper-containing glycosylphosphatidylinositol-linked splice variant of ceruloplasmin in nitrosothiol formation [12].
  • The effects of feeding rats high levels of dietary zinc (240 mg Zn/kg diet) on the activities of the copper-requiring metalloenzymes: ceruloplasmin (Cp), cupro -zinc superoxide dismutase (SOD) and cytochrome c oxidase (CCO) were determined [24].
  • The increase of holo-Cp in acute and chronic hepatitis in LEC rats was explained by the delivery of Cu, accumulating in the non-metallothionein-bound form, to Cp outside the Golgi apparatus of the liver [25].

Analytical, diagnostic and therapeutic context of Cp


  1. Interleukin-1beta up-regulates iron efflux in rat C6 glioma cells through modulation of ceruloplasmin and ferroportin-1 synthesis. di Patti, M.C., Persichini, T., Mazzone, V., Polticelli, F., Colasanti, M., Musci, G. Neurosci. Lett. (2004) [Pubmed]
  2. Rat ceruloplasmin. Molecular cloning and gene expression in liver, choroid plexus, yolk sac, placenta, and testis. Aldred, A.R., Grimes, A., Schreiber, G., Mercer, J.F. J. Biol. Chem. (1987) [Pubmed]
  3. Primary structure of rat ceruloplasmin and analysis of tissue-specific gene expression during development. Fleming, R.E., Gitlin, J.D. J. Biol. Chem. (1990) [Pubmed]
  4. Structural and functional analysis of the 5'-flanking region of the rat ceruloplasmin gene. Fleming, R.E., Gitlin, J.D. J. Biol. Chem. (1992) [Pubmed]
  5. Developmental regulation of hepatic ceruloplasmin mRNA and serum activity by exogenous thyroxine and dexamethasone. Fitch, C.A., Song, Y., Levenson, C.W. Proc. Soc. Exp. Biol. Med. (1999) [Pubmed]
  6. A novel glycosylphosphatidylinositol-anchored form of ceruloplasmin is expressed by mammalian astrocytes. Patel, B.N., David, S. J. Biol. Chem. (1997) [Pubmed]
  7. Role of prostaglandin E1 and copper in angiogenesis. Ziche, M., Jones, J., Gullino, P.M. J. Natl. Cancer Inst. (1982) [Pubmed]
  8. Early cell transplantation in LEC rats modeling Wilson's disease eliminates hepatic copper with reversal of liver disease. Malhi, H., Irani, A.N., Volenberg, I., Schilsky, M.L., Gupta, S. Gastroenterology (2002) [Pubmed]
  9. Wilson's disease gene is homologous to hts causing abnormal copper transport in Long-Evans cinnamon rats. Muramatsu, Y., Yamada, T., Miura, M., Sakai, T., Suzuki, Y., Serikawa, T., Tanzi, R.E., Matsumoto, K. Gastroenterology (1994) [Pubmed]
  10. The effect of portal-systemic shunting on hepatic sex hormone receptors in male rats. Stauber, R.E., Rosenblum, E., Eagon, P.K., Gavaler, J.S., Van Thiel, D.H. Gastroenterology (1991) [Pubmed]
  11. Liver endothelium mediates the hepatocyte's uptake of ceruloplasmin. Tavassoli, M., Kishimoto, T., Kataoka, M. J. Cell Biol. (1986) [Pubmed]
  12. Involvement of glycosylphosphatidylinositol-linked ceruloplasmin in the copper/zinc-nitric oxide-dependent degradation of glypican-1 heparan sulfate in rat C6 glioma cells. Mani, K., Cheng, F., Havsmark, B., David, S., Fransson, L.A. J. Biol. Chem. (2004) [Pubmed]
  13. Regulation of ceruloplasmin by retinoic acid in the developing rat. Song, Y., Levenson, C.W. International journal for vitamin and nutrition research. Internationale Zeitschrift für Vitamin- und Ernährungsforschung. Journal international de vitaminologie et de nutrition. (1997) [Pubmed]
  14. Hypogonadism precedes liver feminization in chronic alcohol-fed male rats. Tadic, S.D., Elm, M.S., Subbotin, V.M., Eagon, P.K. Hepatology (2000) [Pubmed]
  15. Influence of hypertension and dietary copper on indexes of copper status in rats. Garrow, T.A., Clegg, M.S., Metzler, G., Keen, C.L. Hypertension (1991) [Pubmed]
  16. Comparative responses of rats to different copper intakes and modes of supplementation. Klevay, L.M., Saari, J.T. Proc. Soc. Exp. Biol. Med. (1993) [Pubmed]
  17. Expression of a membrane-bound form of the ferroxidase ceruloplasmin by leptomeningeal cells. Mittal, B., Doroudchi, M.M., Jeong, S.Y., Patel, B.N., David, S. Glia (2003) [Pubmed]
  18. Localization of iron metabolism-related mRNAs in rat liver indicate that HFE is expressed predominantly in hepatocytes. Zhang, A.S., Xiong, S., Tsukamoto, H., Enns, C.A. Blood (2004) [Pubmed]
  19. Alternative RNA splicing generates a glycosylphosphatidylinositol-anchored form of ceruloplasmin in mammalian brain. Patel, B.N., Dunn, R.J., David, S. J. Biol. Chem. (2000) [Pubmed]
  20. Dietary iron status has little effect on expression of ceruloplasmin but alters that of ferritin in rats. Tran, T., Ashraf, M., Jones, L., Westbrook, T., Hazegh-Azam, M., Linder, M.C. J. Nutr. (2002) [Pubmed]
  21. Two-dimensional gel analysis of secreted proteins induced by interleukin-1 beta in rat astrocytes. Chang, J.W., Young, D.A., Coleman, P.D., O'Banion, M.K. Neurochem. Int. (2001) [Pubmed]
  22. Zinc status and interleukin-1 beta-induced alterations in mineral metabolism in rats. Bui, L.M., Dressendorfer, R.H., Keen, C.L., Summary, J.J., Dubick, M.A. Proc. Soc. Exp. Biol. Med. (1994) [Pubmed]
  23. Glycosyl phosphatidylinositol-anchored ceruloplasmin is expressed by rat Sertoli cells and is concentrated in detergent-insoluble membrane fractions. Fortna, R.R., Watson, H.A., Nyquist, S.E. Biol. Reprod. (1999) [Pubmed]
  24. The effects of high dietary zinc and copper deficiency on the activity of copper-requiring metalloenzymes in the growing rat. L'Abbé, M.R., Fischer, P.W. J. Nutr. (1984) [Pubmed]
  25. Copper balance and ceruloplasmin in chronic hepatitis in a Wilson disease animal model, LEC rats. Komatsu, Y., Ogra, Y., Suzuki, K.T. Arch. Toxicol. (2002) [Pubmed]
  26. Ceruloplasmin carries the anionic glycan oligo/poly alpha2,8 deaminoneuraminic acid. Ziak, M., Meier, M., Novak-Hofer, I., Roth, J. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
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