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https://www.readbyqxmd.com/read/28737129/association-between-polymorphisms-in-ctr1-ctr2-atp7a-and-atp7b-and-platinum-resistance-in-epithelial-ovarian-cancer
#1
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 CTR1, CTR2, ATP7A, and ATP7B regulate intracellular concentration of platinum by mediating its uptake and efflux in cells. We sought to explore the effect of genetic polymorphisms in CTR1, CTR2, ATP7A, and ATP7B on platinum resistance in patients suffering from epithelial ovarian cancer (EOC). A total of 152 Chinese EOC patients were enrolled in this study, all of whom underwent adjuvant chemotherapy using platinum and taxane after maximal debulking surgery. In total, 11 single-nucleotide polymorphisms (SNPs) in CTR1, CTR2, ATP7A, and ATP7B were genotyped in these patients...
July 24, 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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28579804/expression-of-urinary-mirnas-targeting-nlrs-inflammasomes-in-bladder-cancer
#6
Ettore Mearini, Giulia Poli, Giovanni Cochetti, Andrea Boni, Maria Giulia Egidi, Stefano Brancorsini
AIM OF THE STUDY: Inflammasome, a large complex of NOD-like receptors (NLRs), drives tumor growth and progression. The present study aimed at exploring the alteration in expression of urinary inflammasome-related microRNAs (miRNAs) in bladder cancer (BC). Our previous report demonstrated the up-regulation of NLRs genes (NLRP3, NLRP4, NLRP9 and NAIP) in urine sediments of patients harboring BC. The expression levels of miRNAs targeting these NLRs (miR-146a-5p, miR-106a-5p, miR-17-5p, miR-223-3p, miR-141-3p, miR-19a-3p, miR-145-5p, miR-185-5p) were assayed in the same patient cohort...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28566692/pilot-study-of-64-cu-i-for-pet-imaging-of-melanoma
#7
Lei Jiang, Yingfeng Tu, Xiang Hu, Ande Bao, Hao Chen, Xiaowei Ma, Tim Doyle, Hongcheng Shi, Zhen Cheng
At present, (64)Cu(II) labeled tracers including (64)CuCl2 have been widely applied in the research of molecular imaging and therapy. Human copper transporter 1 (hCTR1) is the major high affinity copper influx transporter in mammalian cells, and specially responsible for the transportation of Cu(I) not Cu(II). Thus, we investigated the feasible application of (64)Cu(I) for PET imaging. (64)Cu(II) was reduced to (64)Cu(I) with the existence of sodium L-ascorbate, DL-Dithiothreitol or cysteine. Cell uptake and efflux assay was investigated using B16F10 and A375 cell lines, respectively...
May 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28543811/the-structural-flexibility-of-the-human-copper-chaperone-atox1-insights-from-combined-pulsed-epr-studies-and-computations
#8
Ariel R Levy, Meital Turgeman, Lada Gevorkyan-Aiapetov, Sharon Ruthstein
Metallochaperones are responsible for shuttling metal ions to target proteins. Thus, a metallochaperone's structure must be sufficiently flexible both to hold onto its ion while traversing the cytoplasm and to transfer the ion to or from a partner protein. Here, we sought to shed light on the structure of Atox1, a metallochaperone involved in the human copper regulation system. Atox1 shuttles copper ions from the main copper transporter, Ctr1, to the ATP7b transporter in the Golgi apparatus. Conventional biophysical tools such as X-ray or NMR cannot always target the various conformational states of metallochaperones, owing to a requirement for crystallography or low sensitivity and resolution...
August 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28516214/interactions-of-cisplatin-and-the-copper-transporter-ctr1-in-human-colon-cancer-cells
#9
Mia C Akerfeldt, Carmen M-N Tran, Clara Shen, Trevor W Hambley, Elizabeth J New
There is much interest in understanding the mechanisms by which platinum-based anticancer agents enter cells, and the copper transporter CTR1 has been the focus of many recent studies. While there is a clinical correlation between CTR1 levels and platinum efficacy, cellular studies have provided conflicting evidence relating to the relationship between cisplatin and CTR1. We report here our studies of the relationship between cisplatin and copper homeostasis in human colon cancer cells. While the accumulation of copper and platinum do not appear to compete with each other, we did observe that cisplatin perturbs CTR1 distribution within 10 min, a far shorter incubation time than commonly employed in cellular studies of cisplatin...
May 17, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28515264/functional-characterization-of-the-copper-transcription-factor-mrpa%C3%A2-from-aspergillus-fumigatus
#10
Yong-Sung Park, Tae-Hyoung Kim, Cheol-Won Yun
Although copper functions as a cofactor in many physiological processes, copper overload leads to harmful effects in living cells. Thus, copper homeostasis is tightly regulated. However, detailed copper metabolic pathways have not yet been identified in filamentous fungi. In this report, we investigated the copper transcription factor AfMac1 (Aspergillus fumigatus Mac1 homologue), and identified its regulatory mechanism in A. fumigatus AfMac1 has domains homologous to the DNA- and copper-binding domains of Mac1 from Saccharomyces cerevisiae , and AfMac1 efficiently complemented Mac1 in S...
May 17, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28511798/induction-of-copper-and-iron-in-acute-cold-stimulated-brown-adipose-tissues
#11
Chao Wang, Xiaojuan Liang, Cong Tao, Xiaolei Yao, Yajun Wang, Yanfang Wang, Kui Li
Copper (Cu) and iron (Fe), the enzymatic cofactors required for various biochemical processes, have been recently linked to lipid metabolism. Adipose tissues play central roles in energy balance and whether copper and iron homeostasis is involved in cold-stimulated energy metabolism remains unknown. In this study, the Cu and Fe contents in interscapular brown adipose tissue (BAT) and subcutaneous white adipose tissue (subWAT) from mice at different developmental stages were measured. Our results revealed the dynamic changes of Cu and Fe levels during development, suggesting their potential roles in energy homeostasis...
May 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28507097/gene-duplication-and-neo-functionalization-in-the-evolutionary-and-functional-divergence-of-the-metazoan-copper-transporters-ctr1-and-ctr2
#12
Brandon L Logeman, L Kent Wood, Jaekwon Lee, Dennis J Thiele
Copper is an essential element for proper organismal development and is involved in a range of processes, including oxidative phosphorylation, neuropeptide biogenesis, and connective tissue maturation. The copper transporter (Ctr) family of integral membrane proteins is ubiquitously found in eukaryotes and mediates the high-affinity transport of Cu(+) across both the plasma membrane and endomembranes. Although mammalian Ctr1 functions as a Cu(+) transporter for Cu acquisition and is essential for embryonic development, a homologous protein, Ctr2, has been proposed to function as a low-affinity Cu transporter, a lysosomal Cu exporter, or a regulator of Ctr1 activity, but its functional and evolutionary relationship to Ctr1 is unclear...
July 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28443323/prevalence-of-ctr1-and-ercc1-polymorphisms-and-response-of-biliary-tract-cancer-to-gemcitabine-platinum-chemotherapy
#13
Skolchart Pongmaneratanakul, Suebpong Tanasanvimon, Thitima Pengsuparp, Nutthada Areepium
Purpose: Biliary tract cancer (BTC)is an aggressive disease with a poor prognosis. Most patients are diagnosed at an advanced stage for which curative surgery is not possible and gemcitabine-platinum chemotherapy is the treatment of choice for advanced cases. Several studies had focused on biomarkers to predict response from platinum drugs in lung cancer, but information is limited for BTC. In this study, two single nucleotide polymorphisms (SNPs) in the copper transporter (CTR1) and excision repair cross-complementary group 1 (ERCC1) genes were investigated as predictive biomarkers of objective response to gemcitabine-platinum...
March 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28421744/a-mini-hip-hop-assay-uncovers-a-central-role-for-copper-and-zinc-in-the-antifungal-mode-of-action-of-allicin
#14
Thomas A K Prescott, Barry Panaretou
Garlic contains the organosulfur compound allicin which exhibits potent antifungal activity. Here we demonstrate the use of a highly simplified yeast chemical genetic screen to characterize its mode of action. By screening 24 validated yeast gene deletion "signature" strains for which hypersensitivity is characteristic for common antifungal modes of action, yeast lacking the high affinity Cu(2+) transporter Ctr1 was found to be hypersensitive to allicin. Focusing on transition metal related genes identified two more hypersensitive strains lacking the Cu(2+) and Zn(2+) transcription factors Mac1 and Zap1...
May 10, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28382507/cisplatin-nephrotoxicity-a-review-of-the-literature
#15
REVIEW
Sandhya Manohar, Nelson Leung
Cisplatin is a platinum containing drug first approved as an antineoplastic agent in 1978. It remains an important and effective therapy in many forms of cancer today. Cisplatin mediates its tumorcidal effects via a number of different cytotoxic mechanisms. Although it is best known for DNA damage, cisplatin also causes cytoplasmic organelle dysfunction particularly with the endoplasmic reticulum and mitochondria. It also activates apoptotic pathways and inflicts cellular damage via oxidative stress and inflammation...
April 5, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28380026/the-role-of-subcutaneous-adipose-tissue-in-supporting-the-copper-balance-in-rats-with-a-chronic-deficiency-in-holo-ceruloplasmin
#16
Ekaterina Y Ilyechova, Nadezhda V Tsymbalenko, Ludmila V Puchkova
We have previously shown that (1) an acute deficiency in blood serum holo-ceruloplasmin (Cp) developed in rats that were fed fodder containing silver ions (Ag-fodder) for one month and (2) the deficiency in holo-Cp was compensated by non-hepatic holo-Cp synthesis in rats that were chronically fed Ag-fodder for 6 months (Ag-rats). The purpose of the present study is to identify the organ(s) that compensate for the hepatic holo-Cp deficiency in the circulation. This study was performed on rats that were fed Ag-fodder (40 mg Ag·kg-1 body mass daily) for 6 months...
2017: PloS One
https://www.readbyqxmd.com/read/28355134/the-interactome-of-the-copper-transporter-atp7a-belongs-to-a-network-of-neurodevelopmental-and-neurodegeneration-factors
#17
Heather S Comstra, Jacob McArthy, Samantha Rudin-Rush, Cortnie Hartwig, Avanti Gokhale, Stephanie A Zlatic, Jessica B Blackburn, Erica Werner, Michael Petris, Priya D'Souza, Parinya Panuwet, Dana Boyd Barr, Vladimir Lupashin, Alysia Vrailas-Mortimer, Victor Faundez
Genetic and environmental factors, such as metals, interact to determine neurological traits. We reasoned that interactomes of molecules handling metals in neurons should include novel metal homeostasis pathways. We focused on copper and its transporter ATP7A because ATP7A null mutations cause neurodegeneration. We performed ATP7A immunoaffinity chromatography and identified 541 proteins co-isolating with ATP7A. The ATP7A interactome concentrated gene products implicated in neurodegeneration and neurodevelopmental disorders, including subunits of the Golgi-localized conserved oligomeric Golgi (COG) complex...
March 29, 2017: ELife
https://www.readbyqxmd.com/read/28293845/kinase-assay-for-constitutive-triple-response-1-ctr1-in-arabidopsis-thaliana
#18
Han Yong Lee, Gyeong Mee Yoon
Protein kinases are central components of signal transduction pathways in the cell. They catalyze the phosphorylation of substrate proteins, resulting in changes of the activity, localization, stability, and protein interactions of the substrates, ultimately coordinating the activity of important cellular processes. CONSTITUTIVE TRIPLE RESPONSE 1 (CTR1) is a Raf-like protein kinase that functions as a negative regulator in the phytohormone ethylene signaling pathway. CTR1 physically interacts with ethylene receptors via its N-terminal domain at the endoplasmic reticulum, and is involved in suppressing ethylene signaling in the absence of ethylene...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28293843/analysis-of-ethylene-receptor-interactions-by-co-immunoprecipitation-assays
#19
Zhiyong Gao, G Eric Schaller
Ethylene receptors are predominantly localized to the endoplasmic reticulum (ER) membrane, and coordinate ethylene signal output through protein-protein interactions with each other and additional signaling components. Here, we describe a co-immunoprecipitation (Co-IP) assay based on the use of the Tandem Affinity Purification (TAP) tag to examine the interactions of ethylene receptors in plant extracts. Human IgG-agarose beads are used to pull down TAP-tagged versions of the protein of interest from detergent extracts of Arabidopsis membranes, and the precipitate then is analyzed immunologically for co-purification of the ethylene receptors...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28115001/host-cell-copper-transporters-ctr1-and-atp7a-are-important-for-influenza-a-virus-replication
#20
Jonathan C Rupp, Manon Locatelli, Alexis Grieser, Andrea Ramos, Patricia J Campbell, Hong Yi, John Steel, Jason L Burkhead, Eric Bortz
BACKGROUND: The essential role of copper in eukaryotic cellular physiology is known, but has not been recognized as important in the context of influenza A virus infection. In this study, we investigated the effect of cellular copper on influenza A virus replication. METHODS: Influenza A/WSN/33 (H1N1) virus growth and macromolecule syntheses were assessed in cultured human lung cells (A549) where the copper concentration of the growth medium was modified, or expression of host genes involved in copper homeostasis was targeted by RNA interference...
January 23, 2017: Virology Journal
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