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Transcriptional regulation of copper metabolism genes in the liver of fetal and neonatal control and iron-deficient rats.

Lenartowicz M, Kennedy C, Hayes H, McArdle HJ - Biometals (2014)

Bottom Line: Atp7b levels, in contrast, decreased from a maximum early in gestation to low levels in the term and post-natal livers.Ceruloplasmin expression appeared to be diametrically opposite to Atp7b.The other two metallochaperones showed the same pattern of expression as Atox1, with a decrease to term, a rise at Day 1, or a rise after birth followed by a brief decrease at about Day 3.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and Evolution, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387, Kraków, Poland.

ABSTRACT
Copper and iron metabolism have been known to interact for many years. We have previously shown, during pregnancy, that copper levels in the maternal liver rise as a consequence of iron deficiency, but that levels in the fetal liver decrease. In this paper, we measure expression of genes involved in copper metabolism in fetal and postnatal liver, to test whether alterations can explain this observation. Additionally, we study the extent to which gene expression changes in the latter stages of pregnancy and in the perinatal period. Ctr1 expression levels dropped to term, rising again thereafter. There was no difference in gene expression between control and iron deficient animals. Atox1 expression remained approximately stable until term, and then there was a rise to a maximum at about Day 8. Atp7a expression levels remained constant, except for a brief drop at term. Atp7b levels, in contrast, decreased from a maximum early in gestation to low levels in the term and post-natal livers. Ceruloplasmin expression appeared to be diametrically opposite to Atp7b. The other two metallochaperones showed the same pattern of expression as Atox1, with a decrease to term, a rise at Day 1, or a rise after birth followed by a brief decrease at about Day 3. None of the genes were significantly affected by iron deficiency, suggesting that changes in expression cannot explain the altered copper levels in the fetal and neonatal liver.

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Related in: MedlinePlus

The model used to study gene expression in this paper. Copper is taken up across the cell membrane, binds to the relevant chaperone and is incorporated into the target protein. More information is given in the text in the relevant section
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Fig1: The model used to study gene expression in this paper. Copper is taken up across the cell membrane, binds to the relevant chaperone and is incorporated into the target protein. More information is given in the text in the relevant section

Mentions: Copper uptake by hepatocytes is mediated by the high affinity copper transporter 1 (CTR1) (Kuo et al. 2001, 2006). In the cell the copper is bound to metallochaperones, and transported to the different compartments of the cell (O’Halloran and Cizewski Culotta 2000). Different chaperones deliver the copper to different enzymes. The copper chaperone of superoxide dismutase (CCS) partitions copper for SOD synthesis (Wong et al. 2000; Bertinato et al. 2003; Prohaska et al. 2003). Copper ions bound to COX 17 chaperone are transported to mitochondria where they are bound to the subunits of the cytochrome-c oxidase (Nevitt et al. 2012; Kako et al. 2004; Punter and Glerum 2003). ATOX1 transport copper to the trans-Golgi network where it is incorporated into the two Cu-transporting ATPases, ATP7A and ATP7B proteins (Barry et al. 2010; Pufahl et al. 1997; Lutsenko et al. 2007, 2008). In hepatocytes, ATP7B delivers copper to ceruloplasmin, a major form of copper in serum. It is also the pathway of excretion of copper into the bile (Huster et al. 2006; La Fontaine et al. 2001; Wijmenga and Klomp 2004). ATP7A is not expressed in the adult liver, but in other tissues is involved in copper excretion and absorption. These data are summarized in Fig. 1. Fig. 1


Transcriptional regulation of copper metabolism genes in the liver of fetal and neonatal control and iron-deficient rats.

Lenartowicz M, Kennedy C, Hayes H, McArdle HJ - Biometals (2014)

The model used to study gene expression in this paper. Copper is taken up across the cell membrane, binds to the relevant chaperone and is incorporated into the target protein. More information is given in the text in the relevant section
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4300417&req=5

Fig1: The model used to study gene expression in this paper. Copper is taken up across the cell membrane, binds to the relevant chaperone and is incorporated into the target protein. More information is given in the text in the relevant section
Mentions: Copper uptake by hepatocytes is mediated by the high affinity copper transporter 1 (CTR1) (Kuo et al. 2001, 2006). In the cell the copper is bound to metallochaperones, and transported to the different compartments of the cell (O’Halloran and Cizewski Culotta 2000). Different chaperones deliver the copper to different enzymes. The copper chaperone of superoxide dismutase (CCS) partitions copper for SOD synthesis (Wong et al. 2000; Bertinato et al. 2003; Prohaska et al. 2003). Copper ions bound to COX 17 chaperone are transported to mitochondria where they are bound to the subunits of the cytochrome-c oxidase (Nevitt et al. 2012; Kako et al. 2004; Punter and Glerum 2003). ATOX1 transport copper to the trans-Golgi network where it is incorporated into the two Cu-transporting ATPases, ATP7A and ATP7B proteins (Barry et al. 2010; Pufahl et al. 1997; Lutsenko et al. 2007, 2008). In hepatocytes, ATP7B delivers copper to ceruloplasmin, a major form of copper in serum. It is also the pathway of excretion of copper into the bile (Huster et al. 2006; La Fontaine et al. 2001; Wijmenga and Klomp 2004). ATP7A is not expressed in the adult liver, but in other tissues is involved in copper excretion and absorption. These data are summarized in Fig. 1. Fig. 1

Bottom Line: Atp7b levels, in contrast, decreased from a maximum early in gestation to low levels in the term and post-natal livers.Ceruloplasmin expression appeared to be diametrically opposite to Atp7b.The other two metallochaperones showed the same pattern of expression as Atox1, with a decrease to term, a rise at Day 1, or a rise after birth followed by a brief decrease at about Day 3.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and Evolution, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387, Kraków, Poland.

ABSTRACT
Copper and iron metabolism have been known to interact for many years. We have previously shown, during pregnancy, that copper levels in the maternal liver rise as a consequence of iron deficiency, but that levels in the fetal liver decrease. In this paper, we measure expression of genes involved in copper metabolism in fetal and postnatal liver, to test whether alterations can explain this observation. Additionally, we study the extent to which gene expression changes in the latter stages of pregnancy and in the perinatal period. Ctr1 expression levels dropped to term, rising again thereafter. There was no difference in gene expression between control and iron deficient animals. Atox1 expression remained approximately stable until term, and then there was a rise to a maximum at about Day 8. Atp7a expression levels remained constant, except for a brief drop at term. Atp7b levels, in contrast, decreased from a maximum early in gestation to low levels in the term and post-natal livers. Ceruloplasmin expression appeared to be diametrically opposite to Atp7b. The other two metallochaperones showed the same pattern of expression as Atox1, with a decrease to term, a rise at Day 1, or a rise after birth followed by a brief decrease at about Day 3. None of the genes were significantly affected by iron deficiency, suggesting that changes in expression cannot explain the altered copper levels in the fetal and neonatal liver.

Show MeSH
Related in: MedlinePlus