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https://www.readbyqxmd.com/read/29139524/computational-modelling-of-the-redistribution-of-copper-isotopes-by-proteins-in-the-liver
#1
Alexander Tennant, Arvi Rauk, Michael E Wieser
Changes in the stable isotope composition of copper in blood serum as a result of biological processes in the liver were quantified as coupled equilibrium fractionation processes. The model used calculated reduced partition function ratios corresponding to interactions involving individual proteins using Density Functional Theory. This quantified the effect that each process had on the redistribution of copper isotopes in the liver. It was not possible to calculate the reduced partition function of CTR1 as a high resolution crystal structure of its copper binding domains are unavailable at the time of writing, and an optimization process was used to estimate the reduced partition function of CTR1 and constrain the possible isotopic fractionation associated with interactions involving CTR1 independent of direct DFT calculations and assumptions of its structure...
November 15, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29134764/peptides-derived-from-histidine-and-methionine-rich-regions-of-copper-transporter-1-exhibit-anti-angiogenic-property-by-chelating-extracellular-cu
#2
Iyer Gomathy Narayanan, K N Sulochana
Angiogenesis is a process of synthesis of new blood vessels from pre-existing vasculature. Copper (Cu) as a micronutrient is important to many proteins for their physiological roles. Cu is transported by ceruloplasmin from liver to other parts of the body. Copper transporter 1 (CTR1) is a transmembrane protein which participitate in Cu transport across the cell. It is also known to be involved in angiogenesis. In this study, we have designed three peptides from copper binding regions of CTR1 which are rich in histidine and methionine...
November 14, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29121854/monitoring-interactions-inside-cells-by-advanced-spectroscopies-overview-of-copper-transporters-and-cisplatin
#3
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 have allowed a deep structural insight into the mode of interaction of platinum drugs with the metal-binding domains of the transporter proteins...
November 10, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29113209/prognostic-value-of-copper-transporter-1-expression-in-patients-with-clear-cell-renal-cell-carcinoma
#4
Yu Xia, Li Liu, Qi Bai, Qilai Long, Jiajun Wang, Wei Xi, Jiejie Xu, Jianming Guo
Clear cell renal cell carcinoma (ccRCC) features a Von Hippel-Lindau mutation, associated with a hypoxia-inducible factor (HIF) imbalance. Copper transporter 1 (CTR1) may also promote tumor progression through the modulation of the HIF pathway by copper. Therefore, the present study explored the prognostic effect of tumor CTR1 expression in patients with ccRCC. A total of 293 patients with ccRCC that underwent nephrectomy were retrospectively enrolled. CTR1 expression was assessed by immunohistochemistry, and its association with clinicopathological features and prognosis were evaluated...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29099786/the-extracellular-domain-of-human-high-affinity-copper-transporter-hndctr1-synthesized-by-e-coli-cells-chelates-silver-and-copper-ions-in-vivo
#5
Tatiana P Sankova, Iurii A Orlov, Andrey N Saveliev, Demid A Kirilenko, Polina S Babich, Pavel N Brunkov, Ludmila V Puchkova
There is much interest in effective copper chelators to correct copper dyshomeostasis in neurodegenerative and oncological diseases. In this study, a recombinant fusion protein for expression in Escherichia coli cells was constructed from glutathione-S-transferase (GST) and the N-terminal domain (ectodomain) of human high affinity copper transporter CTR1 (hNdCTR1), which has three metal-bound motifs. Several biological properties of the GST-hNdCTR1 fusion protein were assessed. It was demonstrated that in cells, the protein was prone to oligomerization, formed inclusion bodies and displayed no toxicity...
November 3, 2017: Biomolecules
https://www.readbyqxmd.com/read/29099271/sox9-mir-130a-ctr1-axis-modulates-ddp-resistance-of-cervical-cancer-cell
#6
Chenzhe Feng, Fang Ma, Chunhong Hu, Jin-An Ma, Jingjing Wang, Yang Zhang, Fang Wu, Tao Hou, Shun Jiang, Yapeng Wang, Yeqian Feng
Cisplatin (DDP) -based chemotherapy is a standard strategy for cervical cancer, while chemoresistance remains a huge challenge. Copper transporter protein 1 (CTR1), a copper influx transporter required for high affinity copper (probably reduced Cu I) transport into the cell, reportedly promotes a significant fraction of DDP internalization in tumor cells. In the present study, we evaluated the function of CTR1 in the cell proliferation of cervical cancer upon DDP treatment. MicroRNAs (miRNAs) have been regarded as essential regulators of cell proliferation, apoptosis, migration, as well as chemoresistance...
November 3, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29042086/effects-of-heat-and-cadmium-exposure-on-stress-related-responses-in-the-liver-of-female-zebrafish-heat-increases-cadmium-toxicity
#7
Sai-Nan Guo, Jia-Lang Zheng, Shuang-Shuang Yuan, Qing-Ling Zhu
In this study, female zebrafish (Danio rerio) were exposed to 26°C or 34°C, 0 or 197μg/L cadmium (Cd), singly or in combination for 7days. Multiple stress-related indicators were evaluated in the liver. Mortality, lipid peroxidation (LPO) and ultrastructural damage increased significantly by Cd exposure alone, and were not affected by heat alone. Interestingly, the combined exposure increased LPO, ultrastructural damage, and mortality compared with Cd exposure alone. The results indicated that elevated temperature increased Cd toxicity, which could be explained by several reasons...
October 14, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28973536/the-mitochondrial-metallochaperone-sco1-maintains-ctr1-at-the-plasma-membrane-to-preserve-copper-homeostasis-in-the-murine-heart
#8
Zakery N Baker, Kimberly Jett, Aren Boulet, Amzad Hossain, Paul A Cobine, Byung-Eun Kim, Amr M El Zawily, Ling Lee, Glen F Tibbits, Michael J Petris, Scot C Leary
SCO1 is a ubiquitously expressed, mitochondrial protein with essential roles in cytochrome c oxidase (COX) assembly and the regulation of copper homeostasis. SCO1 patients present with severe forms of early onset disease, and ultimately succumb from liver, heart or brain failure. However, the inherent susceptibility of these tissues to SCO1 mutations and the clinical heterogeneity observed across SCO1 pedigrees remain poorly understood phenomena. To further address this issue, we generated Sco1hrt/hrt and Sco1stm/stm mice in which Sco1 was specifically deleted in heart and striated muscle, respectively...
September 4, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28965584/identification-of-eight-copper-cu-uptake-related-genes-from-yellow-catfish-pelteobagrus-fulvidraco-and-their-tissue-expression-and-transcriptional-responses-to-dietborne-cu-exposure
#9
Jie Cheng, Zhi Luo, Guang-Hui Chen, Chuan-Chuan Wei, Mei-Qin Zhuo
The present working hypothesis is that absorption of dietary Cu is related to mRNA expressions of genes involved in Cu uptake and transport of the intestine in fish. To this end, the full-length cDNA sequences of eight Cu uptake related genes, including two isoforms of copper transporter genes (ctr1 and ctr2), three copper chaperone genes (atox1, ccs and cox17), two Cu-ATPase genes (atp7a and atp7b) and divalent metal ion transporter 1 (dmt1), were cloned and characterized in yellow catfish P. fulvidraco, respectively...
December 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/28962782/fabrication-of-cellulose-acetate-polybenzoxazine-cross-linked-electrospun-nanofibrous-membrane-for-water-treatment
#10
Yelda Ertas, Tamer Uyar
Herein, polybenzoxazine based cross-linked cellulose acetate nanofibrous membrane exhibiting enhanced thermal/mechanical properties and improved adsorption efficiency was successfully produced via electrospinning and thermal curing. Initially, suitable solution composition was determined by varying the amount of the benzoxazine (BA-a) resin, cellulose acetate (CA) and citric acid (CTR) to obtain uniform nanofibrous membrane via electrospinning. Subsequently, thermal curing was performed by step-wise at 150, 175, 200 and 225°C to obtain cross-linked composite nanofibrous membranes...
December 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28955207/hydrogen-inhalation-protects-against-ototoxicity-induced-by-intravenous-cisplatin-in-the-guinea-pig
#11
Anette E Fransson, Marta Kisiel, Kristian Pirttilä, Curt Pettersson, Pernilla Videhult Pierre, Göran F E Laurell
Introduction: Permanent hearing loss and tinnitus as side-effects from treatment with the anticancer drug cisplatin is a clinical problem. Ototoxicity may be reduced by co-administration of an otoprotective agent, but the results in humans have so far been modest. Aim: The present preclinical in vivo study aimed to explore the protective efficacy of hydrogen (H2) inhalation on ototoxicity induced by intravenous cisplatin. Materials and Methods: Albino guinea pigs were divided into four groups. The Cispt (n = 11) and Cispt+H2 (n = 11) groups were given intravenous cisplatin (8 mg/kg b...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28938148/intestinal-epithelial-cell-injury-induced-by-copper-containing-nanoparticles-in-piglets
#12
Hui Zhang, Xiaoxing Wu, Khalid Mehmood, Zhenyu Chang, Kun Li, Xiong Jiang, Fazul Nabi, Muhammad Ijaz, Mujeeb Ur Rehman, Muhammad Tariq Javed, Donghai Zhou
The nano copper has been widely used in modern clinical medicine practice. However, it has been noticed that nano copper particles induce cell injury and toxicity. The present study was designed to determine the effect of nano copper particles on cell injury of intestinal epithelial cells (IECs) in piglets. The IECs were treated with different doses of nano copper (5, 10, 20 and 40μg/ml) for 24-48h to observe cell injury and toxicity. Cell injury was measured based on morphological and other changes including oxidative stress and genes expression...
September 18, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28820536/atp7a-and-atp7b-regulate-copper-homeostasis-in-developing-male-germ-cells-in-mice
#13
Mateusz Ogórek, Małgorzata Lenartowicz, Rafał Starzyński, Aneta Jończy, Robert Staroń, Andrzej Doniec, Wojciech Krzeptowski, Aleksandra Bednarz, Olga Pierzchała, Paweł Lipiński, Zenon Rajfur, Zbigniew Baster, Patrycja Gibas-Tybur, Paweł Grzmil
The maintenance of copper homeostasis is critical for all cells. As learned from mice with disturbed copper metabolism, this trace element is also important for spermatogenesis. The experiments conducted in yeasts have demonstrated that appropriate copper level must be preserved to enable meiosis progression; however, increased copper level is toxic for cells. This study aims to analyze the expression profile of Atp7a and Atp7b and other genes encoding copper-related proteins during spermatogenesis in mice...
September 20, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28805879/downregulation-of-hepatic-multi-drug-resistance-protein-1-mdr1-after-copper-exposure
#14
Sara Reinartz Groba, Sarah Guttmann, Christoph Niemietz, Friedrich Bernick, Vanessa Sauer, Oliver Hachmöller, Uwe Karst, Hans Zischka, Andree Zibert, Hartmut H Schmidt
Copper homeostasis is strictly regulated in mammalian cells. We investigated the adaptation of hepatocytes after long-term copper exposure. Copper-resistant hepatoma HepG2 cell lines lacking ATP7B were generated. Growth, copper accumulation, gene expression, and transport were determined. Hepatocyte-like cells derived from a Wilson disease (WD) patient and the liver of a WD animal model were also studied. The rapidly gained copper resistance was found to be stable, as subculturing of cells in the absence of added copper (weaning) did not restore copper sensitivity...
September 20, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28763775/heat-indicators-of-oxidative-stress-inflammation-and-metal-transport-show-dependence-of-cadmium-pollution-history-in-the-liver-of-female-zebrafish
#15
Qing-Ling Zhu, Sai-Nan Guo, Shuang-Shuang Yuan, Zhen-Ming Lv, Jia-Lang Zheng, Hu Xia
Environmental stressors such as high temperature and metal exposure may occur sequentially, simultaneously, previously in aquatic ecosystems. However, information about whether responses to high temperature depend on Cd exposure history is still unknown in fish. Zebrafish were exposed to 0 (group 1), 2.5 (group 2) and 5μg/L (group 3) cadmium (Cd) for 10 weeks, and then each group was subjected to Cd-free water maintained at 26°C and 32°C for 7days respectively. 26 indicators were used to compare differences between 26°C and 32°C in the liver of female zebrafish, including 5 biochemical indicators (activity of Cu/Zn-SOD, CAT and iNOS; LPO; MT protein), 8 molecular indicators of oxidative stress (mRNA levels of Nrf2, Cu/Zn-SOD, CAT, HSF1, HSF2, HSP70, MTF-1 and MT), 5 molecular indicators of inflammation (mRNA levels of IL-6, IL-1β, TNF-α, iNOS and NF-κB), 8 molecular indicators of metal transport (mRNA levels of, ZnT1, ZnT5, ZIP8, ZIP10, ATP7A, ATP7B and CTR1)...
July 20, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28737129/association-between-polymorphisms-in-ctr1-ctr2-atp7a-and-atp7b-and-platinum-resistance-in-epithelial-ovarian-cancer
#16
Tailin Li, Jingbo Peng, Feiyue Zeng, Keqiang Zhang, Jinyang Liu, Xi Li, Qianying Ouyang, Guo Wang, Liansheng Wang, Zhaoqian Liu, Yingzi Liu
The copper transporters <italic>CTR1</italic>, <italic>CTR2</italic>, <italic>ATP7A</italic>, and <italic>ATP7B</italic> regulate intracellular concentration of platinum by mediating its uptake and efflux in cells. We sought to explore the effect of genetic polymorphisms in <italic>CTR1</italic>, <italic>CTR2</italic>, <italic>ATP7A</italic>, and <italic>ATP7B</italic> on platinum resistance in patients suffering from epithelial ovarian cancer (EOC)...
October 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28714373/targeting-mir-21-decreases-expression-of-multi-drug-resistant-genes-and-promotes-chemosensitivity-of-renal-carcinoma
#17
Kelly Gaudelot, Jean-Baptiste Gibier, Nicolas Pottier, Brigitte Hémon, Isabelle Van Seuningen, François Glowacki, Xavier Leroy, Christelle Cauffiez, Viviane Gnemmi, Sébastien Aubert, Michaël Perrais
Renal cell carcinoma, the most common neoplasm of adult kidney, accounts for about 3% of adult malignancies and is usually highly resistant to conventional therapy. MicroRNAs are a class of small non-coding RNAs, which have been previously shown to promote malignant initiation and progression. In this study, we focused our attention on miR-21, a well described oncomiR commonly upregulated in cancer. Using a cohort of 99 primary renal cell carcinoma samples, we showed that miR-21 expression in cancer tissues was higher than in adjacent non-tumor tissues whereas no significant difference was observed with stages, grades, and metastatic outcome...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28653724/probing-functional-roles-of-wilson-disease-protein-atp7b-copper-binding-domains-in-yeast
#18
Kumaravel Ponnandai Shanmugavel, Dina Petranovic, Pernilla Wittung-Stafshede
After Ctr1-mediated uptake into human cells, copper (Cu) ions are transported by the cytoplasmic Cu chaperone Atox1 to the Wilson disease protein (ATP7B) in the Golgi network. Cu transfer occurs via direct protein-protein interactions and leads to incorporation of Cu into Cu-dependent enzymes. ATP7B is a large multi-domain membrane-spanning protein which, in contrast to homologs, has six cytoplasmic metal-binding domains (MBDs). The reason for multiple MBDs is proposed to be indirect modulation of activity but mechanistic studies of full-length ATP7B are limited...
July 19, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28640195/pharmacogenomic-variants-may-influence-the-urinary-excretion-of-novel-kidney-injury-biomarkers-in-patients-receiving-cisplatin
#19
Cara Chang, Yichun Hu, Susan L Hogan, Nickie Mercke, Madeleine Gomez, Cindy O'Bryant, Daniel W Bowles, Blessy George, Xia Wen, Lauren M Aleksunes, Melanie S Joy
Nephrotoxicity is a dose limiting side effect associated with the use of cisplatin in the treatment of solid tumors. The degree of nephrotoxicity is dictated by the selective accumulation of cisplatin in renal tubule cells due to: (1) uptake by organic cation transporter 2 (OCT2) and copper transporter 1 (CTR1); (2) metabolism by glutathione S-transferases (GSTs) and γ-glutamyltransferase 1 (GGT1); and (3) efflux by multidrug resistance-associated protein 2 (MRP2) and multidrug and toxin extrusion protein 1 (MATE1)...
June 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28583595/the-copper-transporter-slc31a1-ctr1-is-expressed-in-bovine-spermatozoa-and-oocytes-copper-in-ivf-medium-improves-sperm-quality
#20
J P Anchordoquy, J M Anchordoquy, A M Pascua, N Nikoloff, P Peral-García, C C Furnus
Adequate dietary intake of copper (Cu) is required for normal reproductive performance in cattle. The objective of this study was to investigate the pregnancy rates from cattle with deficient, marginal and adequate Cu plasma concentration at the beginning of artificial insemination protocol. Moreover, we determined Cu concentrations present in bovine oviductal fluid (OF), and the effects of Cu on fertilizing ability of bovine spermatozoa. Also, the presence of Cu transporter, SLC31A1 (also known as CTR1), in spermatozoa and in vitro matured oocyte were investigated...
July 15, 2017: Theriogenology
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