To examine the mechanisms of holo-caeruloplasmin biosynthesis, we measured the serum caeruloplasmin concentration and oxidase activity, hepatic caeruloplasmin mRNA content and hepatocyte caeruloplasmin biosynthesis and secretion in normal and copper-deficient rats. Copper deficiency resulted in a near-complete loss of serum caeruloplasmin oxidase activity, yet only a 60% reduction in serum caeruloplasmin concentration and no change in the abundance of hepatic caeruloplasmin mRNA or the rate of caeruloplasmin biosynthesis. Both interleukin-1 alpha and lipopolysaccharide increased hepatic caeruloplasmin mRNA content and caeruloplasmin biosynthesis in normal and copper-deficient animals, but neither mediator increased caeruloplasmin oxidase activity in the copper-deficient group. Pulse-chase studies in primary hepatocytes from normal and copper-deficient rats revealed that the secretory rates for newly synthesized caeruloplasmin were identical, despite little or no holo-caeruloplasmin synthesis in hepatocytes of copper-deficient rats. We conclude that hepatocyte copper content has no effect on hepatic caeruloplasmin-gene expression or caeruloplasmin biosynthesis and that the incorporation of copper into newly synthesized caeruloplasmin is not a rate-limiting step in the biosynthesis or secretion of the apoprotein from rat hepatocytes.
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March 1992
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Research Article|
March 15 1992
Mechanisms of caeruloplasmin biosynthesis in normal and copper-deficient rats
J D Gitlin;
J D Gitlin
*Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, 400 South Kingshighway Boulevard, St. Louis, MO 63110, and Food Science and Human Nutrition Department, University of Florida, Gainesville, FL, U.S.A.
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J J Schroeder;
J J Schroeder
*Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, 400 South Kingshighway Boulevard, St. Louis, MO 63110, and Food Science and Human Nutrition Department, University of Florida, Gainesville, FL, U.S.A.
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L M Lee-Ambrose;
L M Lee-Ambrose
*Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, 400 South Kingshighway Boulevard, St. Louis, MO 63110, and Food Science and Human Nutrition Department, University of Florida, Gainesville, FL, U.S.A.
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R J Cousins
R J Cousins
*Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, 400 South Kingshighway Boulevard, St. Louis, MO 63110, and Food Science and Human Nutrition Department, University of Florida, Gainesville, FL, U.S.A.
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Biochem J (1992) 282 (3): 835–839.
Citation
J D Gitlin, J J Schroeder, L M Lee-Ambrose, R J Cousins; Mechanisms of caeruloplasmin biosynthesis in normal and copper-deficient rats. Biochem J 15 March 1992; 282 (3): 835–839. doi: https://doi.org/10.1042/bj2820835
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