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Feng Chen, Zhi Luo, Guang-Hui Chen, Xi Shi, Xu Liu, Yu-Feng Song, Ya-Xiong Pan
The present study was conducted to explore the effects of waterborne Cu exposure on intestinal Cu transport and lipid metabolism of Synechogobius hasta. S. hasta were exposed to 0, 0.4721 and 0.9442μM Cu, respectively. Sampling occurred on days 0, 21 and 42, respectively. Growth performance, intestinal lipid deposition, Cu content, and activities and mRNA expression of enzymes and genes involved in Cu transport and lipid metabolism were analyzed. Cu exposure decreased WG and SGR on days 21 and 42. Cu exposure increased intestinal Cu and lipid contents...
September 2016: Aquatic Toxicology
Feng Chen, Zhi Luo, Yao-Fang Fan, Kun Wu, Ya-Xiong Pan, Xu Liu, Li-Han Zhang, Yu-Feng Song
Two isoforms of Cu transporter (CTR1 and CTR2) and metallothionein (MT1 and MT2), and divalent metal ion transporter 1 (DMT1) were cloned and characterized in Synechogobius hasta, respectively. The protein sequences of S. hasta CTRs possessed two methionine-rich regions (MxM and MxxxM) and three transmembrane regions. At the C-terminus, CTR1 contained a sequence of conserved cysteine and histidine residues (HCH), while CTR2 did not contain the conserved sequence. The protein sequence of S. hasta DMT1 possessed all the characteristic features of DMT1, including twelve conserved hydrophobic cores of transmembrane domains...
September 2016: Chemosphere
Kristin M Bompiani, Cheng-Yu Tsai, Felix P Achatz, Janika K Liebig, Stephen B Howell
The development of resistance to cisplatin (cDDP) is commonly accompanied by reduced drug uptake or increased efflux. Previous studies in yeast and murine embryonic fibroblasts have reported that the copper (Cu) transporters and chaperones participate in the uptake, efflux, and intracellular distribution of cDDP. However, there is conflicting data from studies in human cells. We used CRISPR-Cas9 genome editing to individually knock out the human copper transporters CTR1 and CTR2 and the copper chaperones ATOX1 and CCS...
September 1, 2016: Metallomics: Integrated Biometal Science
Deepak Kilari, Elizabeth Guancial, Eric S Kim
Platinum (Pt)-based antitumor agents are effective in the treatment of many solid malignancies. However, their efficacy is limited by toxicity and drug resistance. Reduced intracellular Pt accumulation has been consistently shown to correlate with resistance in tumors. Proteins involved in copper homeostasis have been identified as Pt transporters. In particular, copper transporter receptor 1 (CTR1), the major copper influx transporter, has been shown to play a significant role in Pt resistance. Clinical studies demonstrated that expression of CTR1 correlated with intratumoral Pt concentration and outcomes following Pt-based therapy...
February 10, 2016: World Journal of Clinical Oncology
Yulia A Zatulovskaia, Ekaterina Y Ilyechova, Ludmila V Puchkova
Strong interest in copper homeostasis is due to the fact that copper is simultaneously a catalytic co-factor of the vital enzymes, a participant in signaling, and a toxic agent provoking oxidative stress. In mammals, during development copper metabolism is conformed to two types. In embryonic type copper metabolism (ETCM), newborns accumulate copper to high level in the liver because its excretion via bile is blocked; and serum copper concentration is low because ceruloplasmin (the main copper-containing protein of plasma) gene expression is repressed...
2015: PloS One
Ariadne Stavare Leal Araujo, Manuel de Jesus Simões, Carina Verna, Ricardo Santos Simões, José Maria Soares Júnior, Edmund Chada Baracat, Regina Célia Teixeira Gomes
OBJECTIVE: To quantify the collagen fibers in the lacrimal gland of female mice with hyperprolactinemia. METHODS: Forty adult female mice were randomly divided into two groups with 20 animals each: nonpregnant control (CTR1, control group, 0.2 mL of saline solution) and nonpregnant experimental (HPRL1, experimental group, 200 µg/day metoclopramide). Treatments lasted for 50 consecutive days. On day 50, 10 females from each group (control and experimental) were euthanized in the proestrus phase; then, the blood was collected and the lacrimal glands were removed...
September 2015: Clinics
Helena Öhrvik, Brandon Logeman, Glyn Noguchi, Inger Eriksson, Lena Kjellén, Dennis J Thiele, Gunnar Pejler
Copper (Cu) is essential for multiple cellular functions. Cellular uptake of Cu(+) is carried out by the Ctr1 high-affinity Cu transporter. The mobilization of endosomal Cu pools is regulated by a protein structurally similar to Ctr1, called Ctr2. It was recently shown that ablation of Ctr2 caused an increase in the concentration of Cu localized to endolysosomes. However, the biological significance of excess endolysosomal Cu accumulation has not been assessed. In this study, we addressed this issue by investigating the impact of Ctr2 deficiency on mast cells, a cell type unusually rich in endolysosomal organelles (secretory granules)...
October 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Cheng-Yu Tsai, Janika K Liebig, Igor F Tsigelny, Stephen B Howell
Mammalian cells have two influx Cu transporters that form trimers in membranes. CTR1 is the high affinity transporter that resides largely in the plasma membrane, and CTR2 is the low affinity transporter that is primarily associated with vesicular structures inside the cell. The major differences between CTR1 and CTR2 are that CTR1 contains a HIS/MET-rich domain N-terminal of the METS that participate in the first two stacked rings that form the pore, and a longer C-terminal tail that includes a Cu binding HIS-CYS-HIS (HCH) motif right at the end...
November 2015: Metallomics: Integrated Biometal Science
Xiangpeng Leng, Qian Mu, Xiaomin Wang, Xiaopeng Li, Xudong Zhu, Lingfei Shangguan, Jinggui Fang
With more copper and copper-containing compounds used as bactericides and fungicides in viticulture, copper homeostasis in grapevine (Vitis) has become one of the serious environmental crises with great risk. To better understand the regulation of Cu homeostasis in grapevine, grapevine seedlings cultured in vitro with different levels of Cu were utilized to investigate the tolerance mechanisms of grapevine responding to copper availability at physiological and molecular levels. The results indicated that Cu contents in roots and leaves arose with increasing levels of Cu application...
November 2015: Functional & Integrative Genomics
Jicheng Zhang, Zhiyong Peng, Donald Maberry, Jacob Volpe, Jeremy D Kimmel, William J Federspiel, John A Kellum
BACKGROUND/AIMS: Hemoadsorption may improve outcomes for sepsis by removing circulating cytokines. We tested a new sorbent used for hemoadsorption. METHODS: CTR sorbent beads were filled into columns of three sizes: CTR0.5 (0.5 ml), CTR1 (1.0 ml) and CTR2 (2.0 ml) and tested using IL-6 capture in vitro. Next, rats were subjected to cecal ligation and puncture and randomly assigned to hemoadsorption with CTR0.5, CTR1, CTR2 or sham treatment. Plasma biomarkers were measured...
2015: Blood Purification
Megan Peccarelli, Taylor D Scott, Hoifung Wong, Xuya Wang, Bessie W Kebaara
The nonsense-mediated mRNA decay (NMD) pathway was originally identified as a pathway that degrades mRNAs with premature termination codons; however, NMD is now known to regulate natural mRNAs as well. Natural mRNAs are degraded by NMD due to the presence of specific NMD targeting features. An atypically long 3'-UTR is one of the features that has been shown to induce the rapid degradation of mRNAs by NMD in Saccharomyces cerevisiae and other organisms. S. cerevisiae CTR2 mRNAs have long 3'-UTRs and are sensitive to NMD, although the extent by which these long 3'-UTRs target the CTR2 mRNAs to the pathway is unknown...
November 2014: Biochimica et Biophysica Acta
Christoffel F J Spies, Julia C Meitz-Hopkins, Shaun D Langenhoven, Mathys C Pretorius, Adéle McLeod
Phytophthora citrophthora from citrus in eastern Corsica and Spain consists of distinct clonal lineages. In South Africa the extent of genetic variation among citrus-associated P. citrophthora isolates is unknown. This was investigated with isolates from South Africa (n =60), Spain (n =10) and six isolates representing three P. citrophthora groups CTR1, CTR2 and CTR3 previously identified with isozyme polymorphisms (Mchau and Coffey 1994). South African and Spanish isolates belonged to two lineages (G1, G2) based on an internal transcribed spacer (ITS) phylogeny, random amplified microsatellites (RAMS) and random amplified polymorphic DNA (RAPD) profiling...
November 2014: Mycologia
Vanessa Galleggiante, Monica Rutigliano, Fabio Sallustio, Domenico Ribatti, Pasquale Ditonno, Carlo Bettocchi, Francesco Paolo Selvaggi, Giuseppe Lucarelli, Michele Battaglia
PURPOSE: In clear cell renal cell carcinoma tissue samples we identified and characterized a population of renal cell carcinoma derived CD133+/CD24+ cancer cells. We studied differences between these cells and their nonneoplastic counterpart, tubular adult renal progenitor cells. MATERIALS AND METHODS: CD133+/CD24+ renal cell carcinoma derived cells were isolated from 40 patients. The mesenchymal phenotype and stemness proteomic profile of these renal cell carcinoma derived cells were characterized...
December 2014: Journal of Urology
Shaoping Zhang, Hong Liu, Greeshma V Amarsingh, Carlos C H Cheung, Sebastian Hogl, Umayal Narayanan, Lin Zhang, Selina McHarg, Jingshu Xu, Deming Gong, John Kennedy, Bernard Barry, Yee Soon Choong, Anthony R J Phillips, Garth J S Cooper
BACKGROUND: Heart disease is the leading cause of death in diabetic patients, and defective copper metabolism may play important roles in the pathogenesis of diabetic cardiomyopathy (DCM). The present study sought to determine how myocardial copper status and key copper-proteins might become impaired by diabetes, and how they respond to treatment with the Cu (II)-selective chelator triethylenetetramine (TETA) in DCM. METHODS: Experiments were performed in Wistar rats with streptozotocin (STZ)-induced diabetes with or without TETA treatment...
2014: Cardiovascular Diabetology
Monika Schweigel-Röntgen
The solute carriers families 30 (SLC30; ZnT), 39 (SLC39; ZIP), and 31 (SLC31; CTR) are involved in the essential maintenance of cellular zinc (Zn²⁺) and copper (Cu²⁺) homeostasis, respectively. ZnTs mediate Zn²⁺ extrusion from cells (SLC30A1) or transport Zn²⁺ into organelles and secretory vesicles/granules (SLC30A2-SLC30A8). SLC39 family members are predominantly localized to the cell membrane where they perform Zn²⁺ uptake and increase the availability of cytosolic Zn²⁺. SLC39A1 is ubiquitously expressed, whereas other ZIP transporters (e...
2014: Current Topics in Membranes
Helena Öhrvik, Dennis J Thiele
Copper (Cu) is an essential metal for growth and development that has the potential to be toxic if levels accumulate beyond the ability of cells to homeostatically balance uptake with detoxification. One system for Cu acquisition is the integral membrane Cu(+) transporter, Ctr1, which has been quite well characterized in terms of its function and physiology. The mammalian Ctr2 protein has been a conundrum for the copper field, as it is structurally closely related to the high affinity Cu transporter Ctr1, sharing important motifs for Cu transport activity...
2015: Journal of Trace Elements in Medicine and Biology
Carlos P Huang, Mariama Fofana, Jefferson Chan, Christopher J Chang, Stephen B Howell
Mammalian cells express two copper (Cu) influx transporters, CTR1 and CTR2. CTR1 serves as an influx transporter for both Cu and cisplatin (cDDP). In mouse embryo fibroblasts, reduction of CTR1 expression renders cells resistant to cDDP whereas reduction of CTR2 makes them hypersensitive both in vitro and in vivo. To investigate the role of CTR2 on intracellular Cu and cDDP sensitivity its expression was molecularly altered in the human epithelial 2008 cancer cell model. Intracellular exchangeable Cu(+) was measured with the fluorescent probe Coppersensor-3 (CS3)...
March 2014: Metallomics: Integrated Biometal Science
Giuliano Ciarimboli
The clinical use of the efficient chemotherapeutic drug cisplatin is limited by its specific severe organ toxicities such as nephro-, oto-, and also peripheral neurotoxicity. Membrane transporters such as the copper transporter-1 (Ctr1), the copper transporter-2 (Ctr2), the P-type copper-transporting ATPases ATP7A and ATP7B, the organic cation transporter-2 (OCT2), and the multidrug extrusion transporter-1 (MATE1) mediate cellular transport of cisplatin. Since OCT2 is specifically expressed in the kidneys, its role as possible target of specific organ protection against undesired cisplatin toxicity is under investigation...
January 2014: Anticancer Research
Simon Leclerc, Kevin J Wilkinson
The bioavailability of a small silver nanoparticle (nAg; nominal size of 5 nm with a polyacrylate coating) by the green alga C. reinhardtii was investigated in order to assess the contributions of Ag(+) and nAg to cellular internalization. Upon exposure to nAg, Ag biouptake exceeded what was predicted based upon measured Ag(+) concentrations. Indeed, although Ag biouptake was greatly reduced when excess cysteine was added to the nAg, it was nonetheless significantly above control levels. For both exposures to nAg and Ag(+), expression levels of the Copper Transport Protein 2 (CTR2) indicated that Ag biouptake could be attributed to the internalization of Ag(+)...
2014: Environmental Science & Technology
Giuliano Ciarimboli
Transporters are important mediators of specific cellular uptake and thus, not only for effects, but also for side effects, metabolism, and excretion of many drugs such as cisplatin. Cisplatin is a potent cytostatic drug, whose use is limited by its severe acute and chronic nephro-, oto-, and peripheral neurotoxicity. For this reason, other platinum derivatives, such as carboplatin and oxaliplatin, with less toxicity but still with antitumoral action have been developed. Several transporters, which are expressed on the cell membranes, have been associated with cisplatin transport across the plasma membrane and across the cell: the copper transporter 1 (Ctr1), the copper transporter 2 (Ctr2), the P-type copper-transporting ATPases ATP7A and ATP7B, the organic cation transporter 2 (OCT2), and the multidrug extrusion transporter 1 (MATE1)...
2012: Scientifica
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