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Hepatic caeruloplasmin-gene expression during development in the guinea-pig. Correlation with changes in hepatic
C D Bingle1, O Epstein, S K Srai
1Department of Protein and Molecular Biology, Royal Free Hospital School of Medicine, London, U.K.
Insights
Neonatal mammals, including guinea pigs, exhibit low serum caeruloplasmin (hypocaeruloplasminaemia). This study reveals caeruloplasmin gene expression begins after birth, coinciding with falling liver copper and rising serum levels.
Area of Science:
- Biochemistry
- Developmental Biology
- Molecular Biology
Background:
- Hypocaeruloplasminaemia, or low serum caeruloplasmin, is a common trait in neonatal mammals.
- Caeruloplasmin is a vital copper-binding protein with critical roles in copper metabolism.
Purpose of the Study:
- To investigate the molecular mechanisms behind hypocaeruloplasminaemia in neonatal guinea pigs.
- To understand the developmental regulation of caeruloplasmin gene expression and its relation to copper metabolism.
Main Methods:
- Northern-blot analysis of guinea pig liver RNA to detect caeruloplasmin mRNA species.
- Gel-filtration chromatography to analyze serum copper binding before and after birth.
Main Results:
- Two caeruloplasmin mRNA species were identified in guinea pig liver.
- Caeruloplasmin mRNA expression initiated postnatally, linked to falling hepatic copper and rising serum levels.
- Serum copper shifted from low-molecular-mass species to caeruloplasmin postnatally.
Conclusions:
- Postnatal initiation of caeruloplasmin gene expression is a key factor in neonatal hypocaeruloplasminaemia.
- Developmental changes in copper metabolism and caeruloplasmin synthesis are tightly regulated.
- Inter-animal variation in mRNA levels suggests additional regulatory factors may be involved.
Abstract:
Decreased amounts of the serum copper-binding protein caeruloplasmin (hypocaeruloplasminaemia) are one of the characteristic abnormalities of copper metabolism that are found in all neonatal mammals. In the present study we have investigated the mechanism responsible for hypocaeruloplasminaemia found in neonatal guinea pigs. Northern-blot analysis of guinea-pig liver RNA revealed the presence of two caeruloplasmin mRNA species. A marked developmental change in expression was observed, with no detectable mRNA before birth, when hepatic copper is elevated. Expression was initiated soon after birth, when copper levels in the liver are falling, and was closely linked to the rise in enzymic activity and protein levels in serum. There was no differential regulation of the two mRNA species; however, a marked inter-animal variation in mRNA levels was observed. Using gel-filtration chromatography we were able to show that, before birth, serum copper was associated with a low-molecular-mass species and that, with the advent of expression of the caeruloplasmin gene after birth, copper was increasingly associated with caeruloplasmin.
