Developmental changes in the expression of the <i>Atp7a</i> gene in the liver of mice during the postnatal period

Lenartowicz, Małgorzata; Wieczerzak, Krzysztof; Krzeptowski, Wojciech; Dobosz, Paula; Grzmil, Paweł; Starzyński, Rafał R.; Lipiński, Paweł

doi:10.1002/jez.586

Cited by 21 publications

(15 citation statements)

References 35 publications

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“…Similar to the age-dependent localization observed for Ctr1 in intestinal epithelial cells [111], hepatic expression of mammalian Atp7a diminishes during the life span of animals reared under Cu adequacy during development from birth into adulthood [120, 121]. This is consistent with measurements of hepatic Cu stores, which reach a maximum around birth and decline progressively thereafter [120, 122, 123].…”

Section: Hepatic Copper Storage Excretion and Role In Systemic Coppesupporting

confidence: 76%

Charting the travels of copper in eukaryotes from yeast to mammals

Nevitt¹,

Öhrvik²,

Thiele³

2012

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

247

248

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Throughout evolution, all organisms have harnessed the redox properties of copper (Cu) and iron (Fe) as a cofactor or structural determinant of proteins that perform critical functions in biology. At its most sobering stance to Earth’s biome, Cu biochemistry allows photosynthetic organisms to harness solar energy and convert it into the organic energy that sustains the existence of all nonphotosynthetic life forms. The conversion of organic energy, in the form of nutrients that include carbohydrates, amino acids and fatty acids, is subsequently released during cellular respiration, itself a Cu-dependent process, and stored as ATP that is used to drive a myriad of critical biological processes such as enzyme-catalyzed biosynthetic processes, transport of cargo around cells and across membranes, and protein degradation. The life-supporting properties of Cu incur a significant challenge to cells that must not only exquisitely balance intracellular Cu concentrations, but also chaperone this redox-active metal from its point of cellular entry to its ultimate destination so as to avert the potential for inappropriate biochemical interactions or generation of damaging reactive oxidative species (ROS). In this review we chart the travels of Cu from the extracellular milieu of fungal and mammalian cells, its path within the cytosol as inferred by the proteins and ligands that escort and deliver Cu to intracellular organelles and protein targets, and its journey throughout the body of mammals.

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Section: Hepatic Copper Storage Excretion and Role In Systemic Coppesupporting

confidence: 76%

Charting the travels of copper in eukaryotes from yeast to mammals

Nevitt¹,

Öhrvik²,

Thiele³

2012

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

247

248

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“…Also we observed the Atp7a gene repression and Atp7b gene activation at the end of ETCM ( Fig 3 ). This observation agrees with the data obtained earlier in other laboratories [ 71 , 72 ].…”

Section: Discussionsupporting

confidence: 94%

The Features of Copper Metabolism in the Rat Liver during Development

2015

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Strong interest in copper homeostasis is due to the fact that copper is simultaneously a catalytic co-factor of the vital enzymes, a participant in signaling, and a toxic agent provoking oxidative stress. In mammals, during development copper metabolism is conformed to two types. In embryonic type copper metabolism (ETCM), newborns accumulate copper to high level in the liver because its excretion via bile is blocked; and serum copper concentration is low because ceruloplasmin (the main copper-containing protein of plasma) gene expression is repressed. In the late weaning, the ETCM switches to the adult type copper metabolism (ATCM), which is manifested by the unlocking of copper excretion and the induction of ceruloplasmin gene activity. The considerable progress has been made in the understanding of the molecular basis of copper metabolic turnover in the ATCM, but many aspects of the copper homeostasis in the ETCM remain unclear. The aim of this study was to investigate the copper metabolism during transition from the ETCM (up to 12-days-old) to the ATCM in the rats. It was shown that in the liver, copper was accumulated in the nuclei during the first 5 days of life, and then it was re-located to the mitochondria. In parallel with the mitochondria, copper bulk bound with cytosolic metallothionein was increased. All compartments of the liver cells rapidly lost most of their copper on the 13th day of life. In newborns, serum copper concentration was low, and its major fraction was associated with holo-Cp, however, a small portion of copper was bound to extracellular metallothionein and a substance that was slowly eluted during gel-filtration. In adults, serum copper concentration increased by about a factor of 3, while metallothionein-bound copper level decreased by a factor of 2. During development, the expression level of Cp, Sod1, Cox4i1, Atp7b, Ctr1, Ctr2, Cox17, and Ccs genes was significantly increased, and metallothionein was decreased. Atp7a gene’s activity was fully repressed. The copper routes in newborns are discussed.

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“…This is the first study to compare Atp7b and Atp7a expression levels in the liver of fetal and neonatal animals. Previous work from our laboratories showed developmental regulation of Atp7a expression in the liver of neonatal mice (Lenartowicz et al 2010 , 2011 ) but little is known about expression pattern of Atp7b in the liver. Here, we show that in the liver of the neonatal rats Atp7a expression dropped in the perinatal period, but then stabilised, while Atp7b expression remained low.…”

Section: Discussionmentioning

confidence: 96%

“…Anti-oxidant 1 protein (ATOX1) (Klomp et al 1997 ), transports Cu to ATP7A and ATP7B, the Cu-transport ATPases (Lutsenko et al 2007 , 2008 ; Van den Berghe and Klomp 2010 ). In adult liver, ATP7A expression is extremely low (Lenartowicz et al 2010 ). However, in the fetus and neonate, both ATPases are expressed.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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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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Developmental changes in the expression of the Atp7a gene in the liver of mice during the postnatal period

Cited by 21 publications

References 35 publications

Charting the travels of copper in eukaryotes from yeast to mammals

Charting the travels of copper in eukaryotes from yeast to mammals

The Features of Copper Metabolism in the Rat Liver during Development

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

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