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

Author(s):  
Ludmila V. Puchkova ◽  
Polina S. Babich ◽  
Yulia A. Zatulovskaia ◽  
Ekaterina Y. Ilyechova ◽  
Francesca Di Sole

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.

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1591 ◽  
Author(s):  
Ludmila Puchkova ◽  
Polina Babich ◽  
Yulia Zatulovskaia ◽  
Ekaterina Ilyechova ◽  
Francesca Di Sole

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.


Genetics ◽  
2000 ◽  
Vol 156 (1) ◽  
pp. 173-182
Author(s):  
George K Christophides ◽  
Ioannis Livadaras ◽  
Charalambos Savakis ◽  
Katia Komitopoulou

Abstract Genes encoding predominantly male-specific serum polypeptides (MSSPs) in the medfly Ceratitis capitata are members of a multigene family that are structurally similar to the genes encoding odorant binding proteins of insects. To study the transcriptional regulation of the genes MSSP-α2 and MSSP-β2, overlapping fragments of their promoters, containing the 5′ UTRs and 5′ flanking regions, were fused to the lacZ reporter gene and introduced into the medfly genome via Minos-mediated germline transformation. Transgenic flies were functionally assayed for β-galactosidase activity. Despite their extensive sequence similarity, the two gene promoters show distinct expression patterns of the reporter gene, consistent with previously reported evidence for analogous transcriptional activity of the corresponding endogenous genes. The MSSP-α2 promoter drives gene expression specifically in the fat body of the adult males, whereas the MSSP-β2 promoter directs gene expression in the midgut of both sexes. In contrast, similar transformation experiments in Drosophila melanogaster showed that both promoters drive the expression of the reporter gene in the midgut of adult flies of both sexes. Thus, the very same MSSP-α2 promoter fragment directs expression in the adult male fat body in Ceratitis, but in the midgut of both sexes in Drosophila. Our data suggest that through the evolution of the MSSP gene family a limited number of mutations that occurred within certain cis-acting elements, in combination with new medfly-specific trans-acting factors, endowed these recently duplicated genes with distinct sex-, tissue-, and temporal-specific expression patterns.


2018 ◽  
Vol 25 (4) ◽  
pp. 462-477 ◽  
Author(s):  
Alessia Lasorsa ◽  
Giovanni Natile ◽  
Antonio Rosato ◽  
Francesco Tadini-Buoninsegni ◽  
Fabio Arnesano

Background: Resistance, either at the onset of the treatment or developed after an initial positive response, is a major limitation of antitumor therapy. In the case of platinum- based drugs, copper transporters have been found to interfere with drug trafficking by facilitating the import or favoring the platinum export and inactivation. Methods: The use of powerful spectroscopic, spectrometric and computational methods has allowed a deep structural insight into the mode of interaction of platinum drugs with the metal-binding domains of the transporter proteins. Results: This review article focuses on the mode in which platinum drugs can compete with copper ion for binding to transport proteins and consequent structural and biological effects. Three types of transporters are discussed in detail: copper transporter 1 (Ctr1), the major responsible for Cu+ uptake; antioxidant-1 copper chaperone (Atox1), responsible for copper transfer within the cytoplasm; and copper ATPases (ATP7A/B), responsible for copper export into specific subcellular compartments and outside the cell. Conclusion: The body of knowledge summarized in this review can help in shaping current chemotherapy to optimize the efficacy of platinum drugs (particularly in relation to resistance) and to mitigate adverse effects on copper metabolism.


2020 ◽  
Vol 10 (2) ◽  
pp. 115-121
Author(s):  
R. N. Mustafin ◽  
E. K. Khusnutdinova

Neurofi bromatosis type I (NF1) is a common hereditary tumour syndrome with autosomal dominant type of inheritance. Average worldwide incidence rate of NF1 is 1:3000, equal in men and women. Th e disease develops with a heterozygous mutation in the oncosupressor neurofi bromin-encoding gene NF1. No NF1-associated most common mutations have been found, with over 1400 mutations being described along the gene. No clinical and genetic correlations are observed for NF1, and its symptoms may vary considerably within same inheritance group. Typical NF1 manifestations include pigmented patches and multiple cutaneous or subcutaneous neurofi bromas, oft en disfi guring in degree. Pathogenetic therapy for NF1 is not yet developed, whilst surgical tumourectomy may lead to recurrence and new tumour development in other localities on the body. Molecular genetic research on putative interfaces with epigenetic factors and gene expression patterns may open promising future avenues. Further, establishing a marker NF1 mutation in NF1 patients will allow secondary prevention of the disease. A survey of russian NF1-related literature reveals prevalence of individual clinical case descriptions. In the Russian Federation, studies of NF1-associated mutations in gene NF1 originate from Moscow and Bashkortostan, which sets off advancement of Bashkir medical genetics and urges further developments. In Bashkortostan, 10 NF1-associated mutations were described from 16 patients. Th e reported mutations с.1278G>A (p.Trp426Х), с.1570G>A (p.Glu540Lys), с.1973_1974delTC (р.Leu658ProfsX10), с.3526_3528delAGA (p.Arg1176del), с.3826delC (р.Arg1276GlufsX8), с.4514+5G>A, c.5758_5761delTTGA (p.Leu1920AsnfsX7) in the NF1 gene are new to science. Further research into other genes’ and microRNA expression in patients with various clinical manifestations of NF1 should be aimed at discovering its possible involvement in disease pathogenesis.


2021 ◽  
Author(s):  
Jie Li ◽  
Pengxing Nie ◽  
Christoph Turck ◽  
Guang-Zhong Wang

Mammalian organs are individually controlled by autonomous circadian clocks. At the molecular level, this process is defined by the cyclical co-expression of both core transcription factors and off-target genes across time. While interactions between these molecular clocks are likely necessary for proper homeostasis, these features remain undefined. Here, we utilize integrative analysis of a baboon diurnal transcriptome atlas to characterize the properties of gene networks under circadian control. We found that 53.4% (8,120) of baboon genes are rhythmically expressed body-wide. In addition, >30% of gene-gene interactions exhibit periodic co-expression patterns, with core circadian genes more cyclically co-expressed than others. Moreover, two basic network modes were observed at the systems level: daytime and nighttime mode. Daytime networks were enriched for genes involved in metabolism, while nighttime networks were enriched for genes associated with growth and cellular signaling. A substantial number of diseases only form significant disease modules at either daytime or nighttime. In addition, we found that 216 of 313 genes encoding products that interact with SARS-CoV-2 are rhythmically expressed throughout the body. Importantly, more than 80% of SARS-CoV-2 related genes enriched modules are rhythmically expressed, and have significant network proximities with circadian regulators. Our data suggest that synchronization amongst circadian gene networks is necessary for proper homeostatic functions and circadian regulators have close interactions with SARS-CoV-2 infection.


1998 ◽  
Vol 111 (19) ◽  
pp. 2967-2975
Author(s):  
D. Riemer ◽  
K. Weber

The chordates combine the vertebrates and the invertebrate phyla of the cephalo- and urochordates (tunicates). Two cytoplasmic intermediate filament (IF) proteins of the urochordate Styela plicata are characterized by cDNA cloning, gene organization, tissue specific expression patterns in the adult animal and the self assembly properties of the recombinant proteins. In line with metazoan phylogeny St-A and St-B have the short length version of the coil 1b domain found in all vertebrate and cephalochordate IF proteins while protostomic IF proteins have the longer length version with an extra 42 residues. St-A is the first IF protein from a lower chordate which can be unambiguously related to a particular vertebrate IF subfamily. St-A shares 46% sequence identity with desmin, displays the N-terminal motif necessary for filament assembly of type III proteins and forms normal homopolymeric 10 nm filaments in vitro. St-A but not St-B is present in smooth muscle cells of the body wall musculature. St-A and St-B are found as separate networks in some interior epithelia. St-B shares 30 to 35% identity with keratin 8, St-A and desmin and does not form IF under in vitro assembly conditions. Its relation to a particular vertebrate IF type or to the eight currently known IF proteins from the cephalochordate Branchiostoma remains unresolved. The striking relation between St-A and desmin predicts that the common progenitor of the urochordate (tunicate) and the cephalochordate/vertebrate lineages already possessed a type III homologue. Unlike in vertebrates intron patterns cannot be used to classify the tunicate IF genes. Although St-A is a type III homologue its gene shows an intron position which in vertebrates is restricted to keratin type II genes.


2004 ◽  
Vol 78 (15) ◽  
pp. 8219-8228 ◽  
Author(s):  
Vincent van Pesch ◽  
Hanane Lanaya ◽  
Jean-Christophe Renauld ◽  
Thomas Michiels

ABSTRACT Mouse and human genomes carry more than a dozen genes coding for closely related alpha interferon (IFN-α) subtypes. IFN-α, as well as IFN-β, IFN-κ, IFN-ε, and limitin, are thought to bind the same receptor, raising the question of whether different IFN subtypes possess specific functions. As some confusion existed in the identity and characteristics of mouse IFN-α subtypes, the availability of data from the mouse genome sequence prompted us to characterize the murine IFN-α family. A total of 14 IFN-α genes were detected in the mouse genome, in addition to three IFN-α pseudogenes. Four IFN-α genes (IFN-α1, IFN-α7/10, IFN-α8/6, and IFN-α11) exhibited surprising allelic divergence between 129/Sv and C57BL/6 mice. All IFN-α subtypes were found to be stable at pH 2 and to exhibit antiviral activity. Interestingly, some IFN subtypes (IFN-α4, IFN-α11, IFN-α12, IFN-β, and limitin) showed higher biological activity levels than others, whereas IFN-α7/10 exhibited lower activity. Most murine IFN-α turned out to be N-glycosylated. However, no correlation was found between N-glycosylation and activity. The various IFN-α subtypes displayed a good correlation between their antiviral and antiproliferative potencies, suggesting that IFN-α subtypes did not diverge primarily to acquire specific biological activities but probably evolved to acquire specific expression patterns. In L929 cells, IFN genes activated in response to poly(I•C) transfection or to viral infection were, however, similar.


Author(s):  
X. Guo ◽  
W. Tan ◽  
C. Wang

Abstract Exosomes, the nanoscale phospholipid bilayer vesicles, enriched in selected proteins, nucleic acids and lipids, which they participated in a variety of biological processes in the body, including physiology and pathology. CircRNAs (circular RNAs) are a class of single-stranded closed molecules with tissue development specific expression patterns that have crucial regulatory functions in various diseases. Non-coding RNAs (such as microRNAs and long non‑coding RNAs) in exosomes have also been shown to play an important regulatory role in humans. However, little research has focused on exosomal circRNAs. Recently, CircRNAs have been identified to be enriched and stably expressed in exosomes. In this review, we summarize the biogenesis and biological functions of exosomes and circRNA, and further revealed the potential role of exosome-derived circRNA in different diseases. Besides, we propose its use as a diagnostic marker and therapeutic punctuation for diseases, especially in cancer.


2019 ◽  
Vol 112 (5) ◽  
pp. 2015-2029 ◽  
Author(s):  
Yali Du ◽  
Kai Xu ◽  
Weihua Ma ◽  
Wenting Su ◽  
Miaomiao Tai ◽  
...  

Abstract Correct gustatory recognition and selection of foods both within and outside the hive by honey bee workers are fundamental to the maintenance of colonies. The tarsal chemosensilla located on the legs of workers are sensitive to nonvolatile compounds and proposed to be involved in gustatory detection. However, little is known about the molecular mechanisms underlying the gustatory recognition of foods in honey bees. In the present study, RNA-seq was performed with RNA samples extracted from the legs of 1-, 10-, and 20-d-old workers of Apis cerana cerana Fabricius, a dominant indigenous crop pollinator with a keen perception ability for phytochemicals. A total of 124 candidate chemosensory proteins (CSPs), including 15 odorant-binding proteins (OBPs), 5 CSPs, 7 gustatory receptors (GRs), 2 sensory neuron membrane proteins (SNMPs), and 95 odorant receptors (ORs), were identified from the assembled leg transcriptome. In silico analysis of expression showed that 36 of them were differentially expressed among the three different ages of A. c. cerana workers. Overall, the genes encoding OBPs and CSPs had great but extremely variable FPKM values and thus were highly expressed in the legs of workers, whereas the genes encoding ORs, GRs, and SNMPs (except SNMP2) were expressed at low levels. Tissue-specific expression patterns indicated that two upregulated genes, AcerOBP15 and AcerCSP3, were predominately expressed in the legs of 20-d-old foragers, suggesting they may play an essential role in gustatory recognition and selection of plant nectars and pollens. This study lays a foundation for further research on the feeding preferences of honey bees.


2019 ◽  
Vol 116 (13) ◽  
pp. 5955-5960 ◽  
Author(s):  
Kerri A. Miller ◽  
Fernando A. Vicentini ◽  
Simon A. Hirota ◽  
Keith A. Sharkey ◽  
Michael E. Wieser

Copper is a critical enzyme cofactor in the body but also a potent cellular toxin when intracellularly unbound. Thus, there is a delicate balance of intracellular copper, maintained by a series of complex interactions between the metal and specific copper transport and binding proteins. The gastrointestinal (GI) tract is the primary site of copper entry into the body and there has been considerable progress in understanding the intricacies of copper metabolism in this region. The GI tract is also host to diverse bacterial populations, and their role in copper metabolism is not well understood. In this study, we compared the isotopic fractionation of copper in the GI tract of mice with intestinal microbiota significantly depleted by antibiotic treatment to that in mice not receiving such treatment. We demonstrated variability in copper isotopic composition along the length of the gut. A significant difference, ∼1.0‰, in copper isotope abundances was measured in the proximal colon of antibiotic-treated mice. The changes in copper isotopic composition in the colon are accompanied by changes in copper transporters. Both CTR1, a copper importer, and ATP7A, a copper transporter across membranes, were significantly down-regulated in the colon of antibiotic-treated mice. This study demonstrated that isotope abundance measurements of metals can be used as an indicator of changes in metabolic processes in vivo. These measurements revealed a host–microbial interaction in the GI tract involved in the regulation of copper transport.


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