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Angel Fernandez I Marti, Christopher A Saski, George A Manganaris, Ksenija Gasic, Carlos H Crisosto
It has recently been described that the Japanese plum "Santa Rosa" bud sport series contains variations in ripening pattern: climacteric, suppressed-climacteric and non-climacteric types. This provides an interesting model to study the role of ethylene and other key mechanisms governing fruit ripening, softening and senescence. The aim of the current study was to investigate such differences at the genomic level, using this series of plum bud sports, with special reference to genes involved in ethylene biosynthesis, signal transduction, and sugar metabolism...
2018: Frontiers in Plant Science
Cristiana Porcu, Laura Antonucci, Barbara Barbaro, Barbara Illi, Sergio Nasi, Maurizio Martini, Anna Licata, Luca Miele, Antonio Grieco, Clara Balsano
Free serum copper correlates with tumor incidence and progression of human cancers, including hepatocellular carcinoma (HCC). Copper extracellular uptake is provided by the transporter CTR1, whose expression is regulated to avoid excessive intracellular copper entry. Inadequate copper serum concentration is involved in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD), which is becoming a major cause of liver damage progression and HCC incidence. Finally, MYC is over-expressed in most of HCCs and is a critical regulator of cellular growth, tumor invasion and metastasis...
February 6, 2018: Oncotarget
Lei Jiang, Dongli Song, Hao Chen, Ao Zhang, Huoqiang Wang, Zhen Cheng
Copper(II) ion (Cu2+ ) is the essential element for numerous pathophysiological processes in vivo. Copper transporter 1 (CTR1) is mainly responsible for maintaining Cu2+ accumulation in cells, which has been found to be over-expressed in inflammatory tissues. Therefore, we explored the potential application of64 CuCl₂ for PET imaging of inflammation through targeting CTR1. The animal models of H₂O₂ induced muscle inflammation and lipopolysaccaharide induced lung inflammation were successfully established, then imaged by small animal PET (PET/CT) post-injection of64 CuCl₂, and PET images were quantitatively analyzed...
February 24, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Maho Konishi, Asuka Imai, Masanori Fujii, Keisuke Sugimoto, Nobuyuki Katakami, Yukihiro Imai, Shingo Kamoshida
Background: Copper transporter 1 (CTR1) is a critical determinant of the uptake and cytotoxic effect of the platinum drugs carboplatin and cisplatin. Thymidylate synthase (TS) is an enzyme involved in DNA synthesis and is associated with resistance of tumor cells to 5-fluorouracil. We investigated the correlation between CTR1 and TS expression levels and treatment outcomes in patients with advanced non-small-cell lung cancer (NSCLC) treated with S-1/carboplatin doublet chemotherapy. Methods: Twenty-nine patients were enrolled in this study...
February 26, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Nadia Maria Berterame, Francesca Martani, Danilo Porro, Paola Branduardi
The yeast Saccharomyces cerevisiae is widely used as a cell factory for the biotechnological production of various industrial products. During these processes, yeasts meet different kinds of stressors that often cause oxidative stress and thus impair cell growth. Therefore, the development of robust strains is indispensable to improve production, yield and productivity of fermentative processes. Copper plays a key role in the response to oxidative stress, as cofactor of the cytosolic superoxide dismutase (Sod1) and being contained in metallochaperone and metallothioneines with antioxidant properties...
February 22, 2018: Metabolic Engineering
I Buß, A Hamacher, N Sarin, M U Kassack, G V Kalayda
Oxaliplatin is a routinely used drug in the treatment of colorectal cancer. However, development of resistance is a major hurdle of the chemotherapy success. Defects in cellular accumulation represent a frequently reported feature of cells with acquired resistance to platinum drugs. Nevertheless, the mechanisms of oxaliplatin uptake and their role in oxaliplatin resistance remain poorly elucidated. The aim of this study was to investigate the relevance of copper transporter 1 (CTR1) and organic cation transporters 1-3 (OCT1-3) for oxaliplatin uptake and resistance to the drug in sensitive and oxaliplatin-resistant ileocecal colorectal adenocarcinoma cells...
February 8, 2018: Metallomics: Integrated Biometal Science
Karolina Bossak, Simon C Drew, Ewelina Stefaniak, Dawid Płonka, Arkadiusz Bonna, Wojciech Bal
Copper Transporter 1 (CTR1) is a homotrimeric membrane protein providing the main route of copper transport into eukaryotic cells from the extracellular milieu. Its N-terminal extracellular domain, rich in His and Met residues, is considered responsible for directing copper into the transmembrane channel. Most of vertebrate CTR1 proteins contain the His residue in position three from N-terminus, creating a well-known Amino Terminal Cu(II)- and Ni(II)-Binding (ATCUN) site. CTR1 from humans, primates and many other species contains the Met-Asp-His (MDH) sequence, while some rodents including mouse have the Met-Asn-His (MNH) N-terminal sequence...
February 2, 2018: Journal of Inorganic Biochemistry
Haibo Pan, Eunhye Kim, Gary O Rankin, Yon Rojanasakul, Youying Tu, Yi Charlie Chen
Ovarian cancer has the highest fatality rate among the gynecologic cancers. The side effects, high relapse rate, and drug resistance lead to low long-term survival rate (less than 40%) of patients with advanced ovarian cancer. Theaflavin-3,3'-digallate (TF3), a black tea polyphenol, showed less cytotoxicity to normal ovarian cells than ovarian cancer cells. We aimed to investigate whether TF3 could potentiate the inhibitory effect of cisplatin against human ovarian cancer cell lines. In the present study, combined treatment with TF3 and cisplatin showed a synergistic cytotoxicity against A2780/CP70 and OVCAR3 cells...
January 2, 2018: International Journal of Molecular Sciences
Verena Schneider, Selim Chaib, Claudia Spanier, Mandy Knapp, Violeta Moscvin, Laura Scordovillo, Alessandra Ewertz, Ulrich Jaehde, Ganna V Kalayda
Combining the multikinase inhibitor sorafenib with the platinum-based chemotherapy of solid tumors was expected to improve treatment outcome. However, in many clinical trials, no benefit from sorafenib addition to the platinum-containing regimen could be demonstrated. Moreover, in some studies, decreased survival of ovarian cancer patients as well as non-small cell lung cancer patients with squamous cell histology was observed. The aim of this study was to investigate the cellular mechanisms of the pharmacological interaction between platinum drugs and sorafenib in different cancer cell lines...
November 30, 2017: AAPS Journal
Prodyot K Chatterjee, Michael M Yeboah, Malvika H Solanki, Gopal Kumar, Xiangying Xue, Valentin A Pavlov, Yousef Al-Abed, Christine N Metz
Acute kidney injury (AKI) is the most common side effect of cisplatin, a widely used chemotherapy drug. Although AKI occurs in up to one third of cancer patients receiving cisplatin, effective renal protective strategies are lacking. Cisplatin targets renal proximal tubular epithelial cells leading to inflammation, reactive oxygen species, tubular cell injury, and eventually cell death. The cholinergic anti-inflammatory pathway is a vagus nerve-mediated reflex that suppresses inflammation via α7 nicotinic acetylcholine receptors (α7nAChRs)...
2017: PloS One
Pan Jiang, Aochang Chen, Xiaoyue Wu, Ming Zhou, Ijaz Ul Haq, Zahula Mariyam, Qing Feng
Long non-coding RNAs (lncRNAs) play significant roles in the pathogenesis of various cancers, including lung cancer. In this study, we aimed to investigate the biological function of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in cancer stem cells (CSCs). CSCs have been suggested as the main cause of tumor metastasis, tumor recurrence and chemotherapy resistance. The copper transporter 1 (CTR1) has been the focus of many recent studies because of its correlation with cisplatin (CDDP) resistance. So far, the mechanism of how NEAT1 regulates CSCs in NSCLC remains unknown...
November 19, 2017: Journal of Cellular Physiology
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
Iyer Gomathy Narayanan, Sulochana K Natarajan
Angiogenesis is a process of synthesis of new blood vessels from preexisting 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 participate 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...
March 2018: Chemical Biology & Drug Design
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
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
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
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
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
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
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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