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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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The Atp7a mRNA profile of the liver of the control and Fe deficient fetus and neonates. The mRNA level is corrected relative to ubiquitin. Values with different letters differ significantly (p < 0.05)
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Fig5: The Atp7a mRNA profile of the liver of the control and Fe deficient fetus and neonates. The mRNA level is corrected relative to ubiquitin. Values with different letters differ significantly (p < 0.05)

Mentions: ATOX1 protein delivers the copper ions to the Golgi apparatus, where they bind to the Cu-transporting ATPases, ATP7A and ATP7B. Both Atp7a and 7b genes were expressed in the fetal liver. Levels dropped to term, and did not change subsequently for Atp7b (Fig. 4). In contrast, Atp7a expression rose briefly at Day 3 (see above for Atox1) thereafter returning to levels seen at Day 0 (Fig. 5). In adult liver, ATP7A expression is negligible. However, in the neonates, expression levels were significantly higher than Atp7b, implying that the former may play a significant role in hepatic copper metabolism in the neonate.Fig. 4


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 Atp7a mRNA profile of the liver of the control and Fe deficient fetus and neonates. The mRNA level is corrected relative to ubiquitin. Values with different letters differ significantly (p < 0.05)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig5: The Atp7a mRNA profile of the liver of the control and Fe deficient fetus and neonates. The mRNA level is corrected relative to ubiquitin. Values with different letters differ significantly (p < 0.05)
Mentions: ATOX1 protein delivers the copper ions to the Golgi apparatus, where they bind to the Cu-transporting ATPases, ATP7A and ATP7B. Both Atp7a and 7b genes were expressed in the fetal liver. Levels dropped to term, and did not change subsequently for Atp7b (Fig. 4). In contrast, Atp7a expression rose briefly at Day 3 (see above for Atox1) thereafter returning to levels seen at Day 0 (Fig. 5). In adult liver, ATP7A expression is negligible. However, in the neonates, expression levels were significantly higher than Atp7b, implying that the former may play a significant role in hepatic copper metabolism in the neonate.Fig. 4

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