Mechanisms of caeruloplasmin biosynthesis in normal and copper-deficient rats.
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.
Gitlin
J D
JD
Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
Schroeder
J J
JJ
Lee-Ambrose
L M
LM
Cousins
R J
RJ
D000818:Animals; D002478:Cells, Cultured; D002570:Ceruloplasmin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D003300:Copper / Q000097:blood / Q000172:deficiency* / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015032:Zinc / Q000097:blood
D012333:RNA, Messenger; D003300:Copper; D002570:Ceruloplasmin; D015032:Zinc