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https://www.readbyqxmd.com/read/29627895/toosendanin-mediates-cisplatin-sensitization-through-targeting-annexin-a4-atp7a-in-non-small-cell-lung-cancer-cells
#1
Mao Dong Zheng, Nai Dong Wang, Xiao Liang Li, Juan Yan, Jian Hua Tang, Xiu Hua Zhao, Zhihua Zhang
Cisplatin (CDDP) is used in the treatment of non-small cell lung cancer (NSCLC), but due to the development of resistance, the benefit has been limited. Toosendanin (TSN) has shown therapeutic effects on NSCLC; however, the role of TSN on CDDP sensitization in NSCLC remains unknown. The antitumor effects of TSN and CDDP sensitization mediated by TSN were explored. TSN was added in various amounts to measure dose- and time-dependent cytotoxicity. Intracellular CDDP was detected by high-performance liquid chromatography...
April 7, 2018: Journal of Natural Medicines
https://www.readbyqxmd.com/read/29599289/interaction-between-the-aaa-atpase-p97-vcp-and-a-concealed-ubx-domain-in-the-copper-transporter-atp7a-is-associated-with-motor-neuron-degeneration
#2
Ling Yi, Stephen G Kaler
The copper-transporting ATPase ATP7A contains eight transmembrane domains and is required for normal human copper homeostasis. Mutations in the ATP7A gene may lead to infantile-onset cerebral degeneration (Menkes disease); occipital horn syndrome (OHS), a related but much milder illness; or an adult-onset isolated distal motor neuropathy. The ATP7A missense mutation T994I is located in the sixth transmembrane domain of ATP7A, represents one of the variants associated with the latter phenotype, and is associated with an abnormal interaction with p97/valosin-containing protein (VCP), a hexameric AAA ATPase (ATPase associated with diverse cellular activities) with multiple biological functions...
March 29, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29594361/mircrorna-139-sensitizes-ovarian-cancer-cell-to-cisplatin-based-chemotherapy-through-regulation-of-atp7a-b
#3
Fang Xiao, Yueran Li, Yajun Wan, Min Xue
PURPOSE: Ovarian cancer remains a most malignant female cancer nowadays. The acquisition of chemoresistance to common-used cisplatin-based chemotherapy results in a decreased overall patient survival. The present study is aimed to investigate the role and mechanism by which miR-139/ ATPases7A/B axis modulates the chemoresistance of ovarian cancer to cisplatin-based chemotherapy. METHODS: The expression of miR-139 in cisplatin-sensitive (n = 23) and cisplatin-resistant (n = 14) ovarian cancer tissues and cell lines (CAOV-3 and SNU119) was determined using real-time PCR assays; its effect on ovarian cancer cell chemoresistance to different concentrations of cisplatin was then assessed by measuring the cell viability using MTT assays...
March 28, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29579719/copper-accumulation-in-senescent-cells-interplay-between-copper-transporters-and-impaired-autophagy
#4
Shashank Masaldan, Sharnel A S Clatworthy, Cristina Gamell, Zoe M Smith, Paul S Francis, Delphine Denoyer, Peter M Meggyesy, Sharon La Fontaine, Michael A Cater
Cellular senescence is characterized by irreversible growth arrest incurred through either replicative exhaustion or by pro-oncogenic cellular stressors (radioactivity, oxidative stress, oncogenic activation). The enrichment of senescent cells in tissues with age has been associated with tissue dyshomeostasis and age-related pathologies including cancers, neurodegenerative disorders (e.g. Alzheimer's, Parkinson's, etc.) and metabolic disorders (e.g. diabetes). We identified copper accumulation as being a universal feature of senescent cells [mouse embryonic fibroblasts (MEF), human prostate epithelial cells and human diploid fibroblasts] in vitro...
March 17, 2018: Redox Biology
https://www.readbyqxmd.com/read/29507920/multimodal-la-icp-ms-and-nanosims-imaging-enables-copper-mapping-within-photoreceptor-megamitochondria-in-a-zebrafish-model-of-menkes-disease
#5
Cheri M Ackerman, Peter K Weber, Tong Xiao, Bao Thai, Tiffani J Kuo, Emily Zhang, Jennifer Pett-Ridge, Christopher J Chang
Copper is essential for eukaryotic life, and animals must acquire this nutrient through the diet and distribute it to cells and organelles for proper function of biological targets. Indeed, mutations in the central copper exporter ATP7A contribute to a spectrum of diseases, including Menkes disease, with symptoms ranging from neurodegeneration to lax connective tissue. As such, a better understanding of the fundamental impacts of ATP7A mutations on in vivo copper distributions is of relevance to those affected by these diseases...
March 6, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29473169/animal-models-of-wilson-disease
#6
REVIEW
Emily Reed, Svetlana Lutsenko, Oliver Bandmann
Wilson disease (WD) is an autosomal recessive disorder of copper metabolism manifesting with hepatic, neurological and psychiatric symptoms. The limitations of the currently available therapy for WD (particularly in the management of neuropsychiatric disease), together with our limited understanding of key aspects of this illness (e.g. neurological vs hepatic presentation) justify the ongoing need to study WD in suitable animal models. Four animal models of WD have been established: the Long-Evans Cinnamon rat, the toxic-milk mouse, the Atp7b knockout mouse and the Labrador retriever...
February 23, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29397366/rare-disease-mechanisms-identified-by-genealogical-proteomics-of-copper-homeostasis-mutant-pedigrees
#7
Stephanie A Zlatic, Alysia Vrailas-Mortimer, Avanti Gokhale, Lucas J Carey, Elizabeth Scott, Reid Burch, Morgan M McCall, Samantha Rudin-Rush, John Bowen Davis, Cortnie Hartwig, Erica Werner, Lian Li, Michael Petris, Victor Faundez
Rare neurological diseases shed light onto universal neurobiological processes. However, molecular mechanisms connecting genetic defects to their disease phenotypes are elusive. Here, we obtain mechanistic information by comparing proteomes of cells from individuals with rare disorders with proteomes from their disease-free consanguineous relatives. We use triple-SILAC mass spectrometry to quantify proteomes from human pedigrees affected by mutations in ATP7A, which cause Menkes disease, a rare neurodegenerative and neurodevelopmental disorder stemming from systemic copper depletion...
January 30, 2018: Cell Systems
https://www.readbyqxmd.com/read/29394468/copper-efflux-transporters-atp7a-and-atp7b-novel-biomarkers-for-platinum-drug-resistance-and-targets-for-therapy
#8
REVIEW
Yue-Qin Li, Ji-Ye Yin, Zhao-Qian Liu, Xiang-Ping Li
Platinum-based chemotherapy agents are widely used in the treatment of various solid malignancies. However, their efficacy is limited by drug resistance. Recent studies suggest that copper efflux transporters, which are encoded by ATP7A and ATP7B, play an important role in platinum drug resistance. Over-expressions of ATP7A and ATP7B are observed in multiple cancers. Moreover, their expressions are associated with cancer prognosis and treatment outcomes of platinum-based chemotherapy. In our review, we highlight the roles of ATP7A/7B in platinum drug resistance and cancer progression...
March 2018: IUBMB Life
https://www.readbyqxmd.com/read/29351582/sco2-mutations-cause-early-onset-axonal-charcot-marie-tooth-disease-associated-with-cellular-copper-deficiency
#9
Adriana P Rebelo, Dimah Saade, Claudia V Pereira, Amjad Farooq, Tyler C Huff, Lisa Abreu, Carlos T Moraes, Diana Mnatsakanova, Kathy Mathews, Hua Yang, Eric A Schon, Stephan Zuchner, Michael E Shy
Recessive mutations in the mitochondrial copper-binding protein SCO2, cytochrome c oxidase (COX) assembly protein, have been reported in several cases with fatal infantile cardioencephalomyopathy with COX deficiency. Significantly expanding the known phenotypic spectrum, we identified compound heterozygous variants in SCO2 in two unrelated patients with axonal polyneuropathy, also known as Charcot-Marie-Tooth disease type 4. Different from previously described cases, our patients developed predominantly motor neuropathy, they survived infancy, and they have not yet developed the cardiomyopathy that causes death in early infancy in reported patients...
March 1, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29333545/dynamic-changes-in-copper-homeostasis-and-post-transcriptional-regulation-of-atp7a-during-myogenic-differentiation
#10
Katherine E Vest, Amanda L Paskavitz, Joseph B Lee, Teresita Padilla-Benavides
Copper (Cu) is an essential metal required for activity of a number of redox active enzymes that participate in critical cellular pathways such as metabolism and cell signaling. Because it is also a toxic metal, Cu must be tightly controlled by a series of transporters and chaperone proteins that regulate Cu homeostasis. The critical nature of Cu is highlighted by the fact that mutations in Cu homeostasis genes cause pathologic conditions such as Menkes and Wilson diseases. While Cu homeostasis in highly affected tissues like the liver and brain is well understood, no study has probed the role of Cu in development of skeletal muscle, another tissue that often shows pathology in these conditions...
February 21, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29325617/wilson-disease-and-related-copper-disorders
#11
Matthew T Lorincz
Copper is a required cofactor for enzymes in critical metabolic pathways. Mutations in copper metabolism genes or abnormalities in copper metabolism result in disease from copper excess or deficiency. Wilson disease (WD) is an autosomal-recessive disease caused by mutations in the ATP7B gene which encodes a copper-transporting ATPase. Over 500 different WD mutations throughout the ATP7B gene have been described, most of which are missense mutations. Mutations in both ATP7B alleles result in abnormal copper metabolism and subsequent toxic accumulation of copper...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29301787/akt2-protein-kinase-b-beta-stabilizes-atp7a-a-copper-transporter-for-extracellular-superoxide-dismutase-in-vascular-smooth-muscle-novel-mechanism-to-limit-endothelial-dysfunction-in-type-2-diabetes-mellitus
#12
Varadarajan Sudhahar, Mustafa Nazir Okur, Zsolt Bagi, John P O'Bryan, Nissim Hay, Ayako Makino, Vijay S Patel, Shane A Phillips, David Stepp, Masuko Ushio-Fukai, Tohru Fukai
OBJECTIVE: Copper transporter ATP7A (copper-transporting/ATPase) is required for full activation of SOD3 (extracellular superoxide dismutase), which is secreted from vascular smooth muscle cells (VSMCs) and anchors to endothelial cell surface to preserve endothelial function by scavenging extracellular superoxide. We reported that ATP7A protein expression and SOD3 activity are decreased in insulin-deficient type 1 diabetes mellitus vessels, thereby, inducing superoxide-mediated endothelial dysfunction, which are rescued by insulin treatment...
March 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29232129/effect-of-structural-modifications-to-glyoxal-bis-thiosemicarbazonato-copper-ii-complexes-on-cellular-copper-uptake-copper-mediated-atp7a-trafficking-and-p-glycoprotein-mediated-efflux
#13
Karla M Acevedo, David J Hayne, Lachlan E McInnes, Asif Noor, Clare Duncan, Diane Moujalled, Irene Volitakis, Angela Rigopoulos, Kevin J Barnham, Victor L Villemagne, Anthony R White, Paul S Donnelly
Bis(thiosemicarbazonato)copper(II) complexes are of interest as potential therapeutics for cancer and neurodegenerative diseases as well as imaging agents for positron emission tomography (PET). The cellular uptake of six bis(thiosemcarbazonato)copper(II)complexes derived from glyoxal, with different functional groups Cu(gtsx) where x = different functional groups, was investigated in SKOV-3, HEK293, and HEK293 P-gp cell lines. Treatment of the cells with the copper complexes increased intracellular copper and increased levels of p-ERK due to activation of the Ras-Raf-MEK-ERK pathway...
February 8, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29168020/copper-chaperone-antioxidant-1-atox-1-is-involved-in-the-induction-of-sod3-in-thp-1-cells
#14
Tetsuro Kamiya, Kosuke Takeuchi, Saki Fukudome, Hirokazu Hara, Tetsuo Adachi
Superoxide dismutase (SOD) 3, a copper (Cu)-containing anti-oxidative enzyme, plays a key role in extracellular redox homeostasis. Cu chaperone antioxidant-1 (Atox-1) not only delivers Cu ions to SOD3 at the trans-Golgi network, it also functions as a transcription factor of SOD3; however, the role of Atox-1 in the regulation of SOD3 during the monocytic differentiation of THP-1 cells has not yet been elucidated. A treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) induced the expression of the Cu transport protein ATP7A in THP-1 cells...
November 22, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/29151946/gene-expression-profiling-reveals-novel-candidate-markers-of-ovarian-carcinoma-intraperitoneal-metastasis
#15
Katerina Elsnerova, Alena Bartakova, Josef Tihlarik, Jiri Bouda, Lukas Rob, Petr Skapa, Martin Hruda, Ivan Gut, Beatrice Mohelnikova-Duchonova, Pavel Soucek, Radka Vaclavikova
Epithelial ovarian cancer (EOC) has the highest mortality among gynecological carcinomas. The lack of specific markers for prognostic determination of EOC progression hinders the search for novel effective therapies. The aim of the present study was (i) to explore differences in expressions of ATP-binding cassette (ABC) and solute carrier (SLC) transporter genes, genes associated with drug metabolism and cell cycle regulation between control ovarian tissues (n = 14), primary EOCs (n = 44) and intraperitoneal metastases (n = 29); (ii) to investigate associations of gene expression levels with prognosis of patients with intraperitoneal metastases...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29121854/monitoring-interactions-inside-cells-by-advanced-spectroscopies-overview-of-copper-transporters-and-cisplatin
#16
REVIEW
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...
February 12, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29112372/tuning-the-color-palette-of-fluorescent-copper-sensors-through-systematic-heteroatom-substitution-at-rhodol-cores
#17
Shang Jia, Karla M Ramos-Torres, Safacan Kolemen, Cheri M Ackerman, Christopher J Chang
Copper is an essential nutrient for sustaining life, and emerging data have expanded the roles of this metal in biology from its canonical functions as a static enzyme cofactor to dynamic functions as a transition metal signal. At the same time, loosely bound, labile copper pools can trigger oxidative stress and damaging events that are detrimental if misregulated. The signal/stress dichotomy of copper motivates the development of new chemical tools to study its spatial and temporal distributions in native biological contexts such as living cells...
November 7, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29080449/peumus-boldus-attenuates-copper-induced-toxicity-in-drosophila-melanogaster
#18
Cláudia Vargas Klimaczewski, Assis Ecker, Bruna Piccoli, Michael Aschner, Nilda Vargas Barbosa, João Batista Teixeira Rocha
Peumus boldus (P. boldus) is a medicinal plant popularly used in the treatment of gastrointestinal disorders. P. boldus aqueous extract is rich in phenolic compounds and alkaloids that possess antiinflammatory and antioxidant effects. In the present study, the potential protective effect of P. boldus against Cu2+ -induced toxicity was investigated. Adult Drosophila melanogaster were exposed to Cu2+ (1mM and 3mM) and/or P. boldus aqueous extract (5mg/mL) in the food during 4days. Cu2+ -fed flies had impairment in the negative geotaxis performance (i...
January 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29058724/a-crispr-screen-identifies-a-pathway-required-for-paraquat-induced-cell-death
#19
Colleen R Reczek, Kıvanç Birsoy, Hyewon Kong, Inmaculada Martínez-Reyes, Tim Wang, Peng Gao, David M Sabatini, Navdeep S Chandel
Paraquat, a herbicide linked to Parkinson's disease, generates reactive oxygen species (ROS), which causes cell death. Because the source of paraquat-induced ROS production remains unknown, we conducted a CRISPR-based positive-selection screen to identify metabolic genes essential for paraquat-induced cell death. Our screen uncovered three genes, POR (cytochrome P450 oxidoreductase), ATP7A (copper transporter), and SLC45A4 (sucrose transporter), required for paraquat-induced cell death. Furthermore, our results revealed POR as the source of paraquat-induced ROS production...
December 2017: Nature Chemical Biology
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
#20
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
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