Biopolym. Cell. 1991; 7(3):24-30.
Molecular defect of biliary excretion of copper in patients with hepatolcnticular degeneration
1Puchkova L. V., 1Verbina I. A., 1Denezhkina V. V., 1Gaitskhoki V. S., 1Neifakh S. A.
  1. Institute of Experimental Medicine, Academy of Medical Sciences of the USSR
    Leningrad, USSR

Abstract

The screening of the samples of blood serum of homo- and heterozygotes with Wilson's disease gene was using immunoelectrophoretic methods. It was shown that patients with Wilsonian gene alongside with normal ceruloplasmin contain in serum ceruloplasmin-like protein too. The same protein was involved into the process of liver cooper secretion in normal subjects. The molecular defect of biliary excretion of copper in patients with Wilson's disease is discussed.

References

[1] Owen CA. Wilson's disease: the etiology, clinical aspects and treatment of inherited copper to toxicosis. New York: Acad, press, 1981. 682 p.
[2] Lekar PG, Makarov VA. hepatolenticular disease. M: Medical, 1984. 204 p.
[3] Sternlieb I, Van den Hamer CJ, Morell AG, Alpert S, Gregoriadis G, Scheinberg IH. Lysosomal defect of hepatic copper excretion in Wilson's disease (hepatolenticular degeneration). Gastroenterology. 1973;64(1):99-105. PubMed
[4] Neifakh SA, Vasiletz IM, Shavlovsky MM. Molecular pathology of ceruloplasmin. Biochem Genet. 1972;6(2):231-8.
[5] Frydman M, Bonné-Tamir B, Farrer LA, Conneally PM, Magazanik A, Ashbel S, Goldwitch Z. Assignment of the gene for Wilson disease to chromosome 13: linkage to the esterase D locus. Proc Natl Acad Sci U S A. 1985;82(6):1819-21.
[6] Figus A, Lampis R, Devoto M, Ristaldi MS, Ideo A, de Virgilis S, Nurchi AM, Corrias A, Corda R, Lai ME, et al. Carrier detection and early diagnosis of Wilson's disease by restriction fragment length polymorphism analysis. J Med Genet. 1989;26(2):78-82.
[7] Yang F, Naylor SL, Lum JB, Cutshaw S, McCombs JL, Naberhaus KH, McGill JR, Adrian GS, Moore CM, Barnett DR, et al. Characterization, mapping, and expression of the human ceruloplasmin gene. Proc Natl Acad Sci U S A. 1986;83(10):3257-61.
[8] Shvartsman AL, VakharlovskiÄ­ VG, GaÄ­tskhoki VS, NeÄ­fakh SA. Molecular structure of the human ceruloplasmin gene and its expression in the Wilson-Konovalov mutation. Dokl Akad Nauk SSSR. 1981;257(3):717-20.
[9] Czaja MJ, Weiner FR, Schwarzenberg SJ, Sternlieb I, Scheinberg IH, Van Thiel DH, LaRusso NF, Giambrone MA, Kirschner R, Koschinsky ML, et al. Molecular studies of ceruloplasmin deficiency in Wilson's disease. J Clin Invest. 1987;80(4):1200-4.
[10] Neifakh SA, Shavlovsky MM. Genetically determined metabolic copper at hepatolenticular degeneration. Progress in med. genetics. M.: Medicine, 1978:106-150.
[11] Gaitskhoki VS. Molecular heterogeneity of human hereditary diseases and problems of their gene therapy. Biopolym Cell. 1990; 6(1):31-46.
[12] Gollan JL, Stocks J, Dormandy TL, Sherlock S. Reduced oxidase activity in the caeruloplasmin of two families with Wilson's disease. J Clin Pathol. 1977;30(1):81-3.
[13] Puchkova LV, Verbina IA, VakharlovskiÄ­ VG, GaÄ­tskhoki VS, NeÄ­fakh SA. Experience in heterozygote detection in Wilson-Konovalov mutation based on the study of molecular forms of ceruloplasmin. Zh Nevropatol Psikhiatr Im S S Korsakova. 1989;89(12):14-8.
[14] Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227(5259):680-5.
[15] Johnson DA, Gautsch JW, Sportsman JR, Elder JH. Improved technique utilizing nonfat dry milk for analysis of proteins and nucleic acids transferred to nitrocellulose. Gene Anal Tech. 1984;1(1):3–8.
[16] Fleischer B, Fleischer S. Glycosidase activity of bovine liver plasma membranes. Biochim Biophys Acta. 1969;183(2):265-75.
[17] A manual of quantitative Immunoelectrophoresis . Eds N. H. Axelsen, J. Kroll, B. Weeke. Oslo; Berger; Tromso: Univ. Storlaget, 1973. 216 p.
[18] Zhikharev SS, Subbotibna TF, Petrova MA, AleÄ­nikova TD, Monakhov NK. Decreased ceruloplasmin levels in the blood serum--an index of atopy in bronchial asthma. Ter Arkh. 1984;56(3):23-6.
[19] Neifakh SA, Vasiliev VB, Shavlovsky MM. Structure, catalytic properties and evolution of ceruloplasmin and other blue proteins. Usp Biol Khim. 1988; 28:102-24.
[20] GaÄ­tskhoki VS, Voronina OV, Denezhkina VV, Pliss MG, Puchkova LV, Shvartsman AL, NeÄ­fakh SA. Expression of ceruloplasmin gene in various organs of the rat. Biokhimiia. 1990;55(5):927-37.
[21] Puchkova LV, Denezhkina VV, Zakharova ET, GaÄ­tskhoki VS, NeÄ­fakh SA. Biosynthesis of ceruloplasmin in various rat organs. Biokhimiia. 1990;55(11):2095-102.
[22] NeÄ­fakh SA, AleÄ­nikova TD, GaÄ­tskhoki VS, Monakhov NK, Puchkova LV. Intracellular proteins--precursors of ceruloplasmin. Dokl Akad Nauk SSSR. 1979;244(1):238-40.
[23] Puchkova LV, VakharlovskiÄ­ VG, GaÄ­tskhoki VS, Monakhov NK, Shvartsman AL. Molecular defect of ceruloplasmin synthesis and maturation in Wilson-Konovalov disease. Genetika. 1982;18(5):703-12.
[24] Puchkova LV, Gaitskhoki VS, L'vov VM et al. Intracellular stages in biosynthesis and maturation of ceruloplasmin. In: Macromolecular in the functioning cell. Ed. A. A. Bayev. Moscow : Nauka, 1982; Pt 2:209-27.
[25] Graul RS, Epstein O, Sherlock S, Scheuer PJ. Immunocytochemical identification of caeruloplasmin in hepatocytes of patients with Wilson's disease. Liver. 1982;2(3):207-11.
[26] Deur CJ, Stone MJ, Frenkel EP. Trace metals in hematopoiesis. Am J Hematol. 1981;11(3):309-31.
[27] Iyengar V, Brewer GJ, Dick RD, Chung OY. Studies of cholecystokinin-stimulated biliary secretions reveal a high molecular weight copper-binding substance in normal subjects that is absent in patients with Wilson's disease. J Lab Clin Med. 1988;111(3):267-74.