Partial Purification of the Rat Erythrocyte Ceruloplasmin Receptor Monitored by an Electrophoresis Mobility Shift Assay

Stern, Robert V.; Frieden, Earl

doi:10.1006/abio.1993.1315

Cited by 7 publications

(3 citation statements)

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“…As concerns the mechanism involved, the concept that Cp-Cu is delivered by direct interaction of Cp with the cell plasma membrane is supported by evidence of Cp “receptors” from research by several independent investigators i.e. there is specific binding of Cp to a variety of whole cells [ 26 , 59 – 62 ] and plasma membrane fractions [ 58 , 63 – 65 ]. (In these studies, most of the binding of labeled Cp was specific, in that it could be inhibited by a large excess of unlabeled Cp.)…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Copper Uptake from Blood Plasma Ceruloplasmin by Mammalian Cells

et al. 2016

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Ceruloplasmin, the main copper binding protein in blood plasma, has been of particular interest for its role in efflux of iron from cells, but has additional functions. Here we tested the hypothesis that it releases its copper for cell uptake by interacting with a cell surface reductase and transporters, producing apoceruloplasmin. Uptake and transepithelial transport of copper from ceruloplasmin was demonstrated with mammary epithelial cell monolayers (PMC42) with tight junctions grown in bicameral chambers, and purified human 64Cu-labeled ceruloplasmin secreted by HepG2 cells. Monolayers took up virtually all the 64Cu over 16h and secreted half into the apical (milk) fluid. This was partly inhibited by Ag(I). The 64Cu in ceruloplasmin purified from plasma of 64Cu-injected mice accumulated linearly in mouse embryonic fibroblasts (MEFs) over 3-6h. Rates were somewhat higher in Ctr1+/+ versus Ctr1-/- cells, and 3-fold lower at 2°C. The ceruloplasmin-derived 64Cu could not be removed by extensive washing or trypsin treatment, and most was recovered in the cytosol. Actual cell copper (determined by furnace atomic absorption) increased markedly upon 24h exposure to holoceruloplasmin. This was accompanied by a conversion of holo to apoceruloplasmin in the culture medium and did not occur during incubation in the absence of cells. Four different endocytosis inhibitors failed to prevent 64Cu uptake from ceruloplasmin. High concentrations of non-radioactive Cu(II)- or Fe(III)-NTA (substrates for cell surface reductases), or Cu(I)-NTA (to compete for transporter uptake) almost eliminated uptake of 64Cu from ceruloplasmin. MEFs had cell surface reductase activity and expressed Steap 2 (but not Steaps 3 and 4 or dCytB). However, six-day siRNA treatment was insufficient to reduce activity or uptake. We conclude that ceruloplasmin is a circulating copper transport protein that may interact with Steap2 on the cell surface, forming apoceruloplasmin, and Cu(I) that enters cells through CTR1 and an unknown copper uptake transporter.

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Section: Introductionmentioning

confidence: 99%

Mechanism of Copper Uptake from Blood Plasma Ceruloplasmin by Mammalian Cells

et al. 2016

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“…In pulse-chase experiments, it has been shown that copper atoms associated with Cp are transferred into the cytosol of non-hepatic cells following the binding of Cp by a protein of the cell membrane [ 109 ]. Candidate proteins for Cp binding include the Cp receptor [ 114 , 115 , 116 ], CTR1 [ 93 ], or STEAP2 [ 94 ]. It was shown that in non-hepatic cells [ 64 Cu]Cp and [ 125 I]-Cp pass on [ 64 Cu] into the cytosol, and the protein moiety (apo-Cp) is absorbed by endocytosis, desyalated in endolysosomal vesicles, and then returned into circulation.…”

Section: Copper Turnover In the Body Of Adult Mammalsmentioning

confidence: 99%

Copper Metabolism of Newborns Is Adapted to Milk Ceruloplasmin as a Nutritive Source of Copper: Overview of the Current Data

et al. 2018

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Copper, which can potentially be a highly toxic agent, is an essential nutrient due to its role as a cofactor for cuproenzymes and its participation in signaling pathways. In mammals, the liver is a central organ that controls copper turnover throughout the body, including copper absorption, distribution, and excretion. In ontogenesis, there are two types of copper metabolism, embryonic and adult, which maintain the balance of copper in each of these periods of life, respectively. In the liver cells, these types of metabolism are characterized by the specific expression patterns and activity levels of the genes encoding ceruloplasmin, which is the main extracellular ferroxidase and copper transporter, and the proteins mediating ceruloplasmin metalation. In newborns, the molecular genetic mechanisms responsible for copper homeostasis and the ontogenetic switch from embryonic to adult copper metabolism are highly adapted to milk ceruloplasmin as a dietary source of copper. In the mammary gland cells, the level of ceruloplasmin gene expression and the alternative splicing of its pre-mRNA govern the amount of ceruloplasmin in the milk, and thus, the amount of copper absorbed by a newborn is controlled. In newborns, the absorption, distribution, and accumulation of copper are adapted to milk ceruloplasmin. If newborns are not breast-fed in the early stages of postnatal development, they do not have this natural control ensuring alimentary copper balance in the body. Although there is still much to be learned about the neonatal consequences of having an imbalance of copper in the mother/newborn system, the time to pay attention to this problem has arrived because the neonatal misbalance of copper may provoke the development of copper-related disorders.

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“…Cp has many functions, and it is classified as a "moonlighting" protein [31]. [101][102][103], CTR1 [72] or STEAP2 [73]. The protein part of Cp, which has given part of its copper atoms (apo-Cp), is absorbed by endocytosis, desyalated in endolysosomal vesicles and then returned to circulation.…”

Section: Copper Turnover In Body Of Adult Mammalsmentioning

confidence: 99%

Copper Metabolism of Newborns Is Adapted to Milk Ceruloplasmin As a Nutritive Source of Copper

Puchkova¹,

Babich²,

Zatulovskaia³

et al. 2018

Preprint

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Copper, which can potentially be a highly toxic agent, is an essential nutrient due to its role as a co-factor for cuproenzymes and participation in signaling pathways. In mammals, the liver is a central organ that controls copper turnover throughout the body: copper absorption, distribution, and excretion. In ontogenesis, there are two types of copper metabolism: embryonic and adult, which maintain the balance of copper in each of these periods, respectively. In the liver cells, these types are characterized by specific expression patterns and activity levels of the genes encoding ceruloplasmin, which is the main extracellular ferroxidase and copper transporter and proteins mediating ceruloplasmin metalation. In newborns, the molecular-genetic mechanisms responsible for copper homeostasis and the ontogenetic switch from embryonic to adult copper metabolism are highly adapted to milk ceruloplasmin as a dietary source of copper. In the mammary gland cells, the level of ceruloplasmin gene expression and the alternative splicing of its pre-mRNA govern the amount of ceruloplasmin in milk, and thus, the amount of copper absorbed by the newborn is controlled. In the newborns, absorption, distribution, and accumulation copper are adapted to milk ceruloplasmin. In the newborns, which are not breast-fed at the early stages of postnatal development, the control for alimentary copper balance is absent. We tried to focus on the neonatal consequences of a violation of the balance of copper in the mother / newborn system. Although there is still much to be learned, the time to pay attention to this problem came because the neonatal misbalance of copper may provoke the development of copper related disorders for future life.

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Partial Purification of the Rat Erythrocyte Ceruloplasmin Receptor Monitored by an Electrophoresis Mobility Shift Assay

Cited by 7 publications

References 0 publications

Mechanism of Copper Uptake from Blood Plasma Ceruloplasmin by Mammalian Cells

Mechanism of Copper Uptake from Blood Plasma Ceruloplasmin by Mammalian Cells

Copper Metabolism of Newborns Is Adapted to Milk Ceruloplasmin as a Nutritive Source of Copper: Overview of the Current Data

Copper Metabolism of Newborns Is Adapted to Milk Ceruloplasmin As a Nutritive Source of Copper

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