Aberrant Expression of ZIP and Znt Zinc Transporters in Urotsa Cells Transformed to Malignant Cells by Cadmium
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Supplemental Information to Mammadova-Bach Et Al., “Laminin Α1 Orchestrates VEGFA Functions in the Ecosystem of Colorectal Carcinogenesis”
Supplemental information to Mammadova-Bach et al., “Laminin α1 orchestrates VEGFA functions in the ecosystem of colorectal carcinogenesis” Supplemental material and methods Cloning of the villin-LMα1 vector The plasmid pBS-villin-promoter containing the 3.5 Kb of the murine villin promoter, the first non coding exon, 5.5 kb of the first intron and 15 nucleotides of the second villin exon, was generated by S. Robine (Institut Curie, Paris, France). The EcoRI site in the multi cloning site was destroyed by fill in ligation with T4 polymerase according to the manufacturer`s instructions (New England Biolabs, Ozyme, Saint Quentin en Yvelines, France). Site directed mutagenesis (GeneEditor in vitro Site-Directed Mutagenesis system, Promega, Charbonnières-les-Bains, France) was then used to introduce a BsiWI site before the start codon of the villin coding sequence using the 5’ phosphorylated primer: 5’CCTTCTCCTCTAGGCTCGCGTACGATGACGTCGGACTTGCGG3’. A double strand annealed oligonucleotide, 5’GGCCGGACGCGTGAATTCGTCGACGC3’ and 5’GGCCGCGTCGACGAATTCACGC GTCC3’ containing restriction site for MluI, EcoRI and SalI were inserted in the NotI site (present in the multi cloning site), generating the plasmid pBS-villin-promoter-MES. The SV40 polyA region of the pEGFP plasmid (Clontech, Ozyme, Saint Quentin Yvelines, France) was amplified by PCR using primers 5’GGCGCCTCTAGATCATAATCAGCCATA3’ and 5’GGCGCCCTTAAGATACATTGATGAGTT3’ before subcloning into the pGEMTeasy vector (Promega, Charbonnières-les-Bains, France). After EcoRI digestion, the SV40 polyA fragment was purified with the NucleoSpin Extract II kit (Machery-Nagel, Hoerdt, France) and then subcloned into the EcoRI site of the plasmid pBS-villin-promoter-MES. Site directed mutagenesis was used to introduce a BsiWI site (5’ phosphorylated AGCGCAGGGAGCGGCGGCCGTACGATGCGCGGCAGCGGCACG3’) before the initiation codon and a MluI site (5’ phosphorylated 1 CCCGGGCCTGAGCCCTAAACGCGTGCCAGCCTCTGCCCTTGG3’) after the stop codon in the full length cDNA coding for the mouse LMα1 in the pCIS vector (kindly provided by P. -
Regulatory Effects of Cu, Zn, and Ca on Fe Absorption: the Intricate Play Between Nutrient Transporters
Nutrients 2013, 5, 957-970; doi:10.3390/nu5030957 OPEN ACCESS nutrients ISSN 2072-6643 www.mdpi.com/journal/nutrients Review Regulatory Effects of Cu, Zn, and Ca on Fe Absorption: The Intricate Play between Nutrient Transporters Nathalie Scheers Division of Life Sciences, Food Science, Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden; E-Mail: [email protected]; Tel.: +46-31-772-3821; Fax: +46-31-772-3830 Received: 4 February 2013; in revised form: 8 March 2013 / Accepted: 15 March 2013 / Published: 20 March 2013 Abstract: Iron is an essential nutrient for almost every living organism because it is required in a number of biological processes that serve to maintain life. In humans, recycling of senescent erythrocytes provides most of the daily requirement of iron. In addition, we need to absorb another 1–2 mg Fe from the diet each day to compensate for losses due to epithelial sloughing, perspiration, and bleeding. Iron absorption in the intestine is mainly regulated on the enterocyte level by effectors in the diet and systemic regulators accessing the enterocyte through the basal lamina. Recently, a complex meshwork of interactions between several trace metals and regulatory proteins was revealed. This review focuses on advances in our understanding of Cu, Zn, and Ca in the regulation of iron absorption. Ascorbate as an important player is also considered. Keywords: iron; absorption; Fe; Zn; Cu; Ca; ascorbate 1. Introduction Iron (Fe) is the second most abundant metal on earth and is a necessity for all life. Iron plays the key role in numerous enzymatic reactions due to its ease in shifting between the two common oxidation states, ferrous (Fe2+) and ferric (Fe3+) iron. -
The Significance of the Evolutionary Relationship of Prion Proteins and ZIP Transporters in Health and Disease
The Significance of the Evolutionary Relationship of Prion Proteins and ZIP Transporters in Health and Disease by Sepehr Ehsani A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Department of Laboratory Medicine and Pathobiology University of Toronto © Copyright by Sepehr Ehsani 2012 The Significance of the Evolutionary Relationship of Prion Proteins and ZIP Transporters in Health and Disease Sepehr Ehsani Doctor of Philosophy Department of Laboratory Medicine and Pathobiology University of Toronto 2012 Abstract The cellular prion protein (PrPC) is unique amongst mammalian proteins in that it not only has the capacity to aggregate (in the form of scrapie PrP; PrPSc) and cause neuronal degeneration, but can also act as an independent vector for the transmission of disease from one individual to another of the same or, in some instances, other species. Since the discovery of PrPC nearly thirty years ago, two salient questions have remained largely unanswered, namely, (i) what is the normal function of the cellular protein in the central nervous system, and (ii) what is/are the factor(s) involved in the misfolding of PrPC into PrPSc? To shed light on aspects of these questions, we undertook a discovery-based interactome investigation of PrPC in mouse neuroblastoma cells (Chapter 2), and among the candidate interactors, identified two members of the ZIP family of zinc transporters (ZIP6 and ZIP10) as possessing a PrP-like domain. Detailed analyses revealed that the LIV-1 subfamily of ZIP transporters (to which ZIPs 6 and 10 belong) are in fact the evolutionary ancestors of prions (Chapter 3). -
Metabolic Hallmarks of Cancer Cells As Targets for Integrative Therapies
Journal of Translational Science Review Article ISSN: 2059-268X Metabolic hallmarks of cancer cells as targets for integrative therapies John Ionescu* and Alexandru Tudor Constantinescu Spezialklinik Neukirchen, Krankenhausstr 9, 93453 Neukirchen, Germany Introduction proteins (ZIP4, ZIP10, LIV-1) is also well documented in cancer cells [15-17]. In 2018, 18.1 million people around the world had cancer, and 9.6 million died from the disease. By 2040, those figures will nearly double Once absorbed in the cell, iron is used on the one hand for the [1]. An increasing body of evidence is suggesting that the reason for synthesis of iron-containing enzymes, on the other hand is stored as this evolution is twofold: on the one hand, environmental, nutritional ferritin complex. and lifestyle factors play an important role in the disease etiology, The high intracellular concentration of transitional metals leads to while, on the other hand, most current therapies are killing tumor and high ROS production via Haber-Weiss and Fenton reactions [4] (Figure healthy cells alike, instead of specifically targeting common metabolic 2), and may be responsible for the considerable genetic variability/ hallmarks of cancer cells. Among the latter we could mention: the heterogeneity of tumor cells, even within the same tumor, among other significant changes of pH and redox potential inside and outside exogenous ROS sources [18-20]. the tumor cells, their energy generating pathways relying on aerobic glycolysis, glutaminolysis or fatty acid oxidation, the activation of the In view of these facts, the widespread clinical prescription of NADPH:quinone-oxidoreductases, as well as the high accumulation iron and zinc preparations for cancer patients appears to be rather of transitional metals and organic pollutants in the tumor tissue counterproductive, as the malignant cells are preferentially supplied accompanied by inactivation of several antioxidative and detox systems. -
Interactions of Zinc with the Intestinal Epithelium - Effects On
Aus dem Institut für Veterinär-Physiologie des Fachbereichs Veterinärmedizin der Freien Universität Berlin Interactions of zinc with the intestinal epithelium - effects on transport properties and zinc homeostasis Inaugural-Dissertation zur Erlangung des Grades eines Doktors der Veterinärmedizin an der Freien U niversität Berlin vorgelegt von Eva-Maria Näser, geb. Gefeller Tierärztin aus Kassel Berlin 2015 Journal-Nr.: 3813 Gefördert durch die Deutsche Forschungsgemeinschaft und die H.W. Schaumann Stiftung Gedruckt mit Genehmigung des Fachbereichs Veterinärmedizin der Freien Universität Berlin Dekan: Univ.-Prof. Dr. Jürgen Zentek Erster Gutachter: Univ.-Prof. Dr. Jörg Rudolf Aschenbach Zweiter Gutachter: Prof. Dr. Holger Martens Dritter Gutachter: Prof. Dr. Robert Klopfleisch Deskriptoren (nach CAB-Thesaurus): pigs, weaning, zinc, intestines, epithelium, jejunum, ion transport Tag der Promotion: 15.09.2015 Bibliografische Information der Deutschen Nationalbibliothek Die Deutsche Nationalbibliothek verzeichnet diese Publikation in der Deutschen Nationalbibliografie; detaillierte bibliografische Daten sind im Internet über <http://dnb.ddb.de> abrufbar. ISBN: 978-3-86387-656-2 Zugl.: Berlin, Freie Univ., Diss., 2015 Dissertation, Freie Universität Berlin D 188 Dieses Werk ist urheberrechtlich geschützt. Alle Rechte, auch die der Übersetzung, des Nachdruckes und der Vervielfältigung des Buches, oder Teilen daraus, vorbehalten. Kein Teil des Werkes darf ohne schriftliche Genehmigung des Verlages in irgendeiner Form reproduziert oder unter Verwendung elektronischer Systeme verarbeitet, vervielfältigt oder verbreitet werden. Die Wiedergabe von Gebrauchsnamen, Warenbezeichnungen, usw. in diesem Werk berechtigt auch ohne besondere Kennzeichnung nicht zu der Annahme, dass solche Namen im Sinne der Warenzeichen- und Markenschutz-Gesetzgebung als frei zu betrachten wären und daher von jedermann benutzt werden dürfen. This document is protected by copyright law. -
Targeting an Nrf2/G6pdh Pathway to Reverse Multi-Drug
TARGETING AN NRF2/G6PDH PATHWAY TO REVERSE MULTI-DRUG RESISTANCE IN DIFFUSE LARGE B-CELL LYMPHOMA A Dissertation by SEYEDHOSSEIN MOUSAVIFARD Submitted to the Office of Graduate and Professional Studies of Texas A&M University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Chair of Committee, Steve Maxwell Committee Members, James C. Sacchettini Raquel Sitcheran David W. Threadgill Warren Zimmer Head of Program, Warren Zimmer May 2017 Major Subject: Medical Sciences Copyright 2017 Seyed Hossein Mousavi-Fard ABSTRACT A leading cause of mortality in diffuse large B-cell lymphoma (DLBCL) patients is the development of resistance to the CHOP regimen, the anthracycline-based chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone. Our first objective of this work was to investigate the impact of Nuclear factor erythroid–related factor 2 (Nrf2)/ glucose-6-phosphate dehydrogenase (G6PDH) pathway on CHOP-resistance in DLBCL cell lines. We provide evidence here that a Nrf2/G6PDH pathway plays a role in mediating CHOP resistance in DLBCL. We found that CHOP-resistant DLBCL cells expressed both higher Nrf2 and G6PDH activities and lower reactive oxygen (predominantly superoxide) levels than CHOP- sensitive cells. We hypothesized that increased activity of the Nrf2/G6PDH pathway leads to higher GSH production, a more reduced state (lower ROS), and CHOP-resistance. In support of our hypothesis, direct inhibition of G6PDH or knockdown of Nrf2/G6PDH lowered both NADPH and GSH levels, increased ROS, and reduced tolerance or CHOP-resistant cells to CHOP. We also present evidence that repeated cycles of CHOP treatment select for a small population of Nrf2High/G6PDHHigh/ROSLow cells that are more tolerant of CHOP and might be responsible for the emergence of chemoresistant tumors. -
Loss of the Dermis Zinc Transporter ZIP13 Promotes the Mildness Of
www.nature.com/scientificreports OPEN Loss of the dermis zinc transporter ZIP13 promotes the mildness of fbrosarcoma by inhibiting autophagy Mi-Gi Lee1,8, Min-Ah Choi2,8, Sehyun Chae3,8, Mi-Ae Kang4, Hantae Jo4, Jin-myoung Baek4, Kyu-Ree In4, Hyein Park4, Hyojin Heo4, Dongmin Jang5, Sofa Brito4, Sung Tae Kim6, Dae-Ok Kim 1,7, Jong-Soo Lee4, Jae-Ryong Kim2* & Bum-Ho Bin 4* Fibrosarcoma is a skin tumor that is frequently observed in humans, dogs, and cats. Despite unsightly appearance, studies on fbrosarcoma have not signifcantly progressed, due to a relatively mild tumor severity and a lower incidence than that of other epithelial tumors. Here, we focused on the role of a recently-found dermis zinc transporter, ZIP13, in fbrosarcoma progression. We generated two transformed cell lines from wild-type and ZIP13-KO mice-derived dermal fbroblasts by stably expressing the Simian Virus (SV) 40-T antigen. The ZIP13−/− cell line exhibited an impairment in autophagy, followed by hypersensitivity to nutrient defciency. The autophagy impairment in the ZIP13−/− cell line was due to the low expression of LC3 gene and protein, and was restored by the DNA demethylating agent, 5-aza-2’-deoxycytidine (5-aza) treatment. Moreover, the DNA methyltransferase activity was signifcantly increased in the ZIP13−/− cell line, indicating the disturbance of epigenetic regulations. Autophagy inhibitors efectively inhibited the growth of fbrosarcoma with relatively minor damages to normal cells in xenograft assay. Our data show that proper control over autophagy and zinc homeostasis could allow for the development of a new therapeutic strategy to treat fbrosarcoma. -
Role of ZIP8 in Host Response to Mycobacterium Tuberculosis
International Journal of Molecular Sciences Review Elemental Ingredients in the Macrophage Cocktail: Role of ZIP8 in Host Response to Mycobacterium tuberculosis Charlie J. Pyle 1, Abul K. Azad 2, Audrey C. Papp 3, Wolfgang Sadee 3, Daren L. Knoell 4,* and Larry S. Schlesinger 2,* 1 Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA; [email protected] 2 Texas Biomedical Research Institute, San Antonio, TX 78227, USA; [email protected] 3 Center for Pharmacogenomics, Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43085, USA; [email protected] (A.C.P.); [email protected] (W.S.) 4 College of Pharmacy, The University of Nebraska Medical Center, Omaha, NE 68198-6120, USA * Correspondence: [email protected] (D.L.K.); [email protected] (L.S.S.); Tel.: +1-402-559-9016 (D.L.K.); +1-210-258-9419 (L.S.S.) Received: 6 October 2017; Accepted: 6 November 2017; Published: 9 November 2017 Abstract: Tuberculosis (TB) is a global epidemic caused by the infection of human macrophages with the world’s most deadly single bacterial pathogen, Mycobacterium tuberculosis (M.tb). M.tb resides in a phagosomal niche within macrophages, where trace element concentrations impact the immune response, bacterial metal metabolism, and bacterial survival. The manipulation of micronutrients is a critical mechanism of host defense against infection. In particular, the human zinc transporter Zrt-/Irt-like protein 8 (ZIP8), one of 14 ZIP family members, is important in the flux of divalent cations, including zinc, into the cytoplasm of macrophages. -
The Role of Zip Superfamily of Metal Transporters in Chronic Diseases, Purification & Characterization of a Bacterial Zip Tr
Wayne State University Wayne State University Theses 1-1-2011 The Role Of Zip Superfamily Of Metal Transporters In Chronic Diseases, Purification & Characterization Of A Bacterial Zip Transporter: Zupt. Iryna King Wayne State University Follow this and additional works at: http://digitalcommons.wayne.edu/oa_theses Part of the Biochemistry Commons, and the Molecular Biology Commons Recommended Citation King, Iryna, "The Role Of Zip Superfamily Of Metal Transporters In Chronic Diseases, Purification & Characterization Of A Bacterial Zip Transporter: Zupt." (2011). Wayne State University Theses. Paper 63. This Open Access Thesis is brought to you for free and open access by DigitalCommons@WayneState. It has been accepted for inclusion in Wayne State University Theses by an authorized administrator of DigitalCommons@WayneState. THE ROLE OF ZIP SUPERFAMILY OF METAL TRANSPORTERS IN CHRONIC DISEASES, PURIFICATION & CHARACTERIZATION OF A BACTERIAL ZIP TRANSPORTER: ZUPT by IRYNA KING THESIS Submitted to the Graduate School of Wayne State University, Detroit, Michigan in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE 2011 MAJOR: BIOCHEMISTRY & MOLECULAR BIOLOGY Approved by: ___________________________________ Advisor Date © COPYRIGHT BY IRYNA KING 2011 All Rights Reserved DEDICATION I dedicate this work to my father, Julian Banas, whose footsteps I indisputably followed into science & my every day inspiration, my son, William Peter King ii ACKNOWLEDGMENTS First and foremost I would like to thank the department of Biochemistry & Molecular Biology at Wayne State University School of Medicine for giving me an opportunity to conduct my research and be a part of their family. I would like to thank my advisor Dr. Bharati Mitra for taking me into the program and nurturing a biochemist in me. -
World Journal of Gastroenterology
World Journal of W J G Gastroenterology Submit a Manuscript: https://www.f6publishing.com World J Gastroenterol 2019 October 14; 25(38): 5732-5772 DOI: 10.3748/wjg.v25.i38.5732 ISSN 1007-9327 (print) ISSN 2219-2840 (online) REVIEW Role of ion channels in gastrointestinal cancer Kyle J Anderson, Robert T Cormier, Patricia M Scott ORCID number: Kyle J Anderson Kyle J Anderson, Robert T Cormier, Patricia M Scott, Department of Biomedical Sciences, (0000-0001-7144-0992); Robert T University of Minnesota Medical School, Duluth, MN 55812, United States Cormier (0000-0003-4423-7053); Patricia M Scott Corresponding author: Patricia M Scott, PhD, Assistant Professor, Department of Biomedical (0000-0002-6336-2653). Sciences, University of Minnesota Medical School, 1035 University Drive, Duluth, MN 55812, United States. [email protected] Author contributions: All authors Telephone: +1-218-726-8361 equally contributed to this paper Fax: +1-218-726-8014 with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version. Abstract In their seminal papers Hanahan and Weinberg described oncogenic processes a Supported by: grants from the normal cell undergoes to be transformed into a cancer cell. The functions of ion National Cancer Institute (NIH R15CA195061A-01), Whiteside channels in the gastrointestinal (GI) tract influence a variety of cellular processes, Institute for Clinical Research, many of which overlap with these hallmarks of cancer. In this review we focus on Essentia Health Systems, Mezin- the roles of the calcium (Ca2+), sodium (Na+), potassium (K+), chloride (Cl-) and Koats Colorectal Cancer zinc (Zn2+) transporters in GI cancer, with a special emphasis on the roles of the Foundation, Randy Shaver Cancer KCNQ1 K+ channel and CFTR Cl- channel in colorectal cancer (CRC). -
Variants in TRIM22 That Affect NOD2 Signaling Are Associated with Very Early Onset Inflammatory Bowel Disease
Accepted Manuscript Variants in TRIM22 that Affect NOD2 Signaling Are Associated With Very Early Onset Inflammatory Bowel Disease Qi Li, Cheng Hiang Lee, Lauren A. Peters, Lucas A. Mastropaolo, Cornelia Thoeni, Abdul Elkadri, Tobias Schwerd, Jun Zhu, Bin Zhang, Yongzhong Zhao, Ke Hao, Antonio Dinarzo, Gabriel Hoffman, Brian A. Kidd, Ryan Murchie, Ziad Al Adham, Conghui Guo, Daniel Kotlarz, Ernest Cutz, Thomas D. Walters, Dror S. Shouval, Mark Curran, Radu Dobrin, Carrie Brodmerkel, Scott B. Snapper, Christoph Klein, John H. Brumell, Mingjing Hu, Ralph Nanan, Brigitte Snanter-Nanan, Melanie Wong, Francoise Le Deist, Elie Haddad, Chaim M. Roifman, Colette Deslandres, Anne M. Griffiths, Kevin J. Gaskin, Holm H. Uhlig, Eric E. Schadt, Aleixo M. Muise PII: S0016-5085(16)00123-2 DOI: 10.1053/j.gastro.2016.01.031 Reference: YGAST 60258 To appear in: Gastroenterology Accepted Date: 22 January 2016 Please cite this article as: Li Q, Lee CH, Peters LA, Mastropaolo LA, Thoeni C, Elkadri A, Schwerd T, Zhu J, Zhang B, Zhao Y, Hao K, Dinarzo A, Hoffman G, Kidd BA, Murchie R, Al Adham Z, Guo C, Kotlarz D, Cutz E, Walters TD, Shouval DS, Curran M, Dobrin R, Brodmerkel C, Snapper SB, Klein C, Brumell JH, Hu M, Nanan R, Snanter-Nanan B, Wong M, Le Deist F, Haddad E, Roifman CM, Deslandres C, Griffiths AM, Gaskin KJ, Uhlig HH, Schadt EE, Muise AM, Variants in TRIM22 that Affect NOD2 Signaling Are Associated With Very Early Onset Inflammatory Bowel Disease, Gastroenterology (2016), doi: 10.1053/j.gastro.2016.01.031. This is a PDF file of an unedited manuscript that has been accepted for publication. -
Evaluation of New Techniques for Zinc and Cortisol
EVALUATION OF NEW TECHNIQUES FOR ZINC AND CORTISOL ASSESSMENT WITH A PLACEBO-CONTROLLED ZINC SUPPLEMENTATION TRIAL IN A SUBSAMPLE OF ETHIOPIAN WOMEN By MAYA LUCIA JORAY Bachelor of Science in Food Technology University of Applied Sciences Wädenswil, Zürich, Switzerland 2001 Master of Science in International Studies Oklahoma State University Stillwater, OK 2004 Submitted to the Faculty of the Graduate College of the Oklahoma State University in partial fulfillment of the requirements for the Degree of DOCTOR OF PHILOSOPHY July, 2011 EVALUATION OF NEW TECHNIQUES FOR ZINC AND CORTISOL ASSESSMENT WITH A PLACEBO-CONTROLLED ZINC SUPPLEMENTATION TRIAL IN A SUBSAMPLE OF ETHIOPIAN WOMEN Dissertation Approved: Dr. B. J. Stoecker Dissertation Adviser Dr. S. L. Clarke Dr. E. Lucas Dr. P. Rayas Duarte Dr. M. E. Payton Interim Dean of the Graduate College ii TABLE OF CONTENTS Chapter Page I. INTRODUCTION ......................................................................................................1 Purpose ....................................................................................................................4 Objective .................................................................................................................5 Null hypotheses ........................................................................................................5 Assumptions and limitations ....................................................................................6 Organization of the dissertation ...............................................................................7