The Abcs of Membrane Transporters in Health and Disease (SLC Series): Introduction Q,Qq ⇑ Matthias A
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Screening and Identification of Key Biomarkers in Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Screening and identification of key biomarkers in clear cell renal cell carcinoma based on bioinformatics analysis Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignancy of the urinary system. The pathogenesis and effective diagnosis of ccRCC have become popular topics for research in the previous decade. In the current study, an integrated bioinformatics analysis was performed to identify core genes associated in ccRCC. An expression dataset (GSE105261) was downloaded from the Gene Expression Omnibus database, and included 26 ccRCC and 9 normal kideny samples. Assessment of the microarray dataset led to the recognition of differentially expressed genes (DEGs), which was subsequently used for pathway and gene ontology (GO) enrichment analysis. -
Small Cell Ovarian Carcinoma: Genomic Stability and Responsiveness to Therapeutics
Gamwell et al. Orphanet Journal of Rare Diseases 2013, 8:33 http://www.ojrd.com/content/8/1/33 RESEARCH Open Access Small cell ovarian carcinoma: genomic stability and responsiveness to therapeutics Lisa F Gamwell1,2, Karen Gambaro3, Maria Merziotis2, Colleen Crane2, Suzanna L Arcand4, Valerie Bourada1,2, Christopher Davis2, Jeremy A Squire6, David G Huntsman7,8, Patricia N Tonin3,4,5 and Barbara C Vanderhyden1,2* Abstract Background: The biology of small cell ovarian carcinoma of the hypercalcemic type (SCCOHT), which is a rare and aggressive form of ovarian cancer, is poorly understood. Tumourigenicity, in vitro growth characteristics, genetic and genomic anomalies, and sensitivity to standard and novel chemotherapeutic treatments were investigated in the unique SCCOHT cell line, BIN-67, to provide further insight in the biology of this rare type of ovarian cancer. Method: The tumourigenic potential of BIN-67 cells was determined and the tumours formed in a xenograft model was compared to human SCCOHT. DNA sequencing, spectral karyotyping and high density SNP array analysis was performed. The sensitivity of the BIN-67 cells to standard chemotherapeutic agents and to vesicular stomatitis virus (VSV) and the JX-594 vaccinia virus was tested. Results: BIN-67 cells were capable of forming spheroids in hanging drop cultures. When xenografted into immunodeficient mice, BIN-67 cells developed into tumours that reflected the hypercalcemia and histology of human SCCOHT, notably intense expression of WT-1 and vimentin, and lack of expression of inhibin. Somatic mutations in TP53 and the most common activating mutations in KRAS and BRAF were not found in BIN-67 cells by DNA sequencing. -
Iron Transport Proteins: Gateways of Cellular and Systemic Iron Homeostasis
Iron transport proteins: Gateways of cellular and systemic iron homeostasis Mitchell D. Knutson, PhD University of Florida Essential Vocabulary Fe Heme Membrane Transport DMT1 FLVCR Ferroportin HRG1 Mitoferrin Nramp1 ZIP14 Serum Transport Transferrin Transferrin receptor 1 Cytosolic Transport PCBP1, PCBP2 Timeline of identification in mammalian iron transport Year Protein Original Publications 1947 Transferrin Laurell and Ingelman, Acta Chem Scand 1959 Transferrin receptor 1 Jandl et al., J Clin Invest 1997 DMT1 Gunshin et al., Nature; Fleming et al. Nature Genet. 1999 Nramp1 Barton et al., J Leukocyt Biol 2000 Ferroportin Donovan et al., Nature; McKie et al., Cell; Abboud et al. J. Biol Chem 2004 FLVCR Quigley et al., Cell 2006 Mitoferrin Shaw et al., Nature 2006 ZIP14 Liuzzi et al., Proc Natl Acad Sci USA 2008 PCBP1, PCBP2 Shi et al., Science 2013 HRG1 White et al., Cell Metab DMT1 (SLC11A2) • Divalent metal-ion transporter-1 • Former names: Nramp2, DCT1 Fleming et al. Nat Genet, 1997; Gunshin et al., Nature 1997 • Mediates uptake of Fe2+, Mn2+, Cd2+ • H+ coupled transporter (cotransporter, symporter) • Main roles: • intestinal iron absorption Illing et al. JBC, 2012 • iron assimilation by erythroid cells DMT1 (SLC11A2) Yanatori et al. BMC Cell Biology 2010 • 4 different isoforms: 557 – 590 a.a. (hDMT1) Hubert & Hentze, PNAS, 2002 • Function similarly in iron transport • Differ in tissue/subcellular distribution and regulation • Regulated by iron: transcriptionally (via HIF2α) post-transcriptionally (via IRE) IRE = Iron-Responsive Element Enterocyte Lumen DMT1 Fe2+ Fe2+ Portal blood Enterocyte Lumen DMT1 Fe2+ Fe2+ Fe2+ Fe2+ Ferroportin Portal blood Ferroportin (SLC40A1) • Only known mammalian iron exporter Donovan et al., Nature 2000; McKie et al., Cell 2000; Abboud et al. -
Cystine–Glutamate Antiporter Xct Deficiency Suppresses Tumor Growth While Preserving Antitumor Immunity
Cystine–glutamate antiporter xCT deficiency suppresses tumor growth while preserving antitumor immunity Michael D. Arensmana, Xiaoran S. Yanga, Danielle M. Leahya, Lourdes Toral-Barzaa, Mary Mileskia, Edward C. Rosfjorda, Fang Wanga, Shibing Dengb, Jeremy S. Myersa, Robert T. Abrahamb, and Christina H. Enga,1 aOncology Research & Development, Pfizer, Pearl River, NY 10965; and bOncology Research & Development, Pfizer, San Diego, CA 92121 Edited by William G. Kaelin Jr., Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, and approved April 2, 2019 (received for review September 1, 2018) T cell-invigorating cancer immunotherapies have near-curative Thus, tumor cells may rely on xCT to fulfill the majority of their potential. However, their clinical benefit is currently limited, as cysteine and GSH needs by importing cystine. only a fraction of patients respond, suggesting that these regimens Inhibition of xCT has been investigated as a therapeutic may benefit from combination with tumor-targeting treatments. As strategy for cancer based on observations that elevated xCT ex- oncogenic progression is accompanied by alterations in metabolic pression on tumor cells correlates with poor prognosis (10–12) pathways, tumors often become heavily reliant on antioxidant and that inhibition of xCT in preclinical studies suppresses tumor machinery and may be susceptible to increases in oxidative stress. growth (10, 12–14). However, these studies relied heavily on the The cystine–glutamate antiporter xCT is frequently overexpressed in use of sulfasalazine, a clinical compound used for the treatment cancer and fuels the production of the antioxidant glutathione; thus, of rheumatoid arthritis, ulcerative colitis, and Crohn’s disease. -
Bioinformatic Analyses of Integral Membrane Transport Proteins Encoded Within the Genome of the Planctomycetes Species, Rhodopirellula Baltica
UC San Diego UC San Diego Previously Published Works Title Bioinformatic analyses of integral membrane transport proteins encoded within the genome of the planctomycetes species, Rhodopirellula baltica. Permalink https://escholarship.org/uc/item/0f85q1z7 Journal Biochimica et biophysica acta, 1838(1 Pt B) ISSN 0006-3002 Authors Paparoditis, Philipp Västermark, Ake Le, Andrew J et al. Publication Date 2014 DOI 10.1016/j.bbamem.2013.08.007 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Biochimica et Biophysica Acta 1838 (2014) 193–215 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbamem Bioinformatic analyses of integral membrane transport proteins encoded within the genome of the planctomycetes species, Rhodopirellula baltica Philipp Paparoditis a, Åke Västermark a,AndrewJ.Lea, John A. Fuerst b, Milton H. Saier Jr. a,⁎ a Department of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA, 92093–0116, USA b School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland, 9072, Australia article info abstract Article history: Rhodopirellula baltica (R. baltica) is a Planctomycete, known to have intracellular membranes. Because of its un- Received 12 April 2013 usual cell structure and ecological significance, we have conducted comprehensive analyses of its transmembrane Received in revised form 8 August 2013 transport proteins. The complete proteome of R. baltica was screened against the Transporter Classification Data- Accepted 9 August 2013 base (TCDB) to identify recognizable integral membrane transport proteins. 342 proteins were identified with a Available online 19 August 2013 high degree of confidence, and these fell into several different classes. -
Upregulation of Peroxisome Proliferator-Activated Receptor-Α And
Upregulation of peroxisome proliferator-activated receptor-α and the lipid metabolism pathway promotes carcinogenesis of ampullary cancer Chih-Yang Wang, Ying-Jui Chao, Yi-Ling Chen, Tzu-Wen Wang, Nam Nhut Phan, Hui-Ping Hsu, Yan-Shen Shan, Ming-Derg Lai 1 Supplementary Table 1. Demographics and clinical outcomes of five patients with ampullary cancer Time of Tumor Time to Age Differentia survival/ Sex Staging size Morphology Recurrence recurrence Condition (years) tion expired (cm) (months) (months) T2N0, 51 F 211 Polypoid Unknown No -- Survived 193 stage Ib T2N0, 2.41.5 58 F Mixed Good Yes 14 Expired 17 stage Ib 0.6 T3N0, 4.53.5 68 M Polypoid Good No -- Survived 162 stage IIA 1.2 T3N0, 66 M 110.8 Ulcerative Good Yes 64 Expired 227 stage IIA T3N0, 60 M 21.81 Mixed Moderate Yes 5.6 Expired 16.7 stage IIA 2 Supplementary Table 2. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of an ampullary cancer microarray using the Database for Annotation, Visualization and Integrated Discovery (DAVID). This table contains only pathways with p values that ranged 0.0001~0.05. KEGG Pathway p value Genes Pentose and 1.50E-04 UGT1A6, CRYL1, UGT1A8, AKR1B1, UGT2B11, UGT2A3, glucuronate UGT2B10, UGT2B7, XYLB interconversions Drug metabolism 1.63E-04 CYP3A4, XDH, UGT1A6, CYP3A5, CES2, CYP3A7, UGT1A8, NAT2, UGT2B11, DPYD, UGT2A3, UGT2B10, UGT2B7 Maturity-onset 2.43E-04 HNF1A, HNF4A, SLC2A2, PKLR, NEUROD1, HNF4G, diabetes of the PDX1, NR5A2, NKX2-2 young Starch and sucrose 6.03E-04 GBA3, UGT1A6, G6PC, UGT1A8, ENPP3, MGAM, SI, metabolism -
Identification of a Novel Nucleobase-Ascorbate Transporter
bioRxiv preprint doi: https://doi.org/10.1101/287870; this version posted December 7, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. 1 Identification of a novel Nucleobase-Ascorbate 2 Transporter family member in fish and amphibians 3 Diogo Oliveira*,1, André M. Machado*,1, Tiago Cardoso1, Mónica Lopes-Marques1, L. Filipe 4 C. Castro1,2● and Raquel Ruivo1● 5 1CIIMAR – Interdisciplinary Centre of Marine and Environmental Research, U. Porto – University 6 of Porto, Porto, Portugal 7 2Department of Biology, Faculty of Sciences, U. Porto - University of Porto, Portugal 8 *Equal contribution 9 ●Corresponding authors at: CIIMAR, Terminal de Cruzeiros do Porto de Leixões, Av. General 10 Norton de Matos s/n, 4450-208 Matosinhos, Portugal. Tel.: +351 223 401 831 11 12 Running title: Novel uric acid transporter in fish and amphibians 13 14 15 bioRxiv preprint doi: https://doi.org/10.1101/287870; this version posted December 7, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. 16 Abstract:Nucleobase-Ascorbate Transporter (NAT) family includes ascorbic acid, nucleobases 17 and uric acid transporters: with a broad evolutionary distribution. In vertebrates, four members 18 have been previously recognized, the ascorbate transporters Slc23a1 and Slc3a2, the nucleobase 19 transporter Slc23a4 and an orphan transporter Slc23a3. -
Cellular Transport Notes About Cell Membranes
Cellular Transport Notes @ 2011 Center for Pre-College Programs, New Jersey Institute of Technology, Newark, New Jersey About Cell Membranes • All cells have a cell membrane • Functions: – Controls what enters and exits the cell to maintain an internal balance called homeostasis TEM picture of a – Provides protection and real cell membrane. support for the cell @ 2011 Center for Pre-College Programs, New Jersey Institute of Technology, Newark, New Jersey 1 About Cell Membranes (continued) 1.Structure of cell membrane Lipid Bilayer -2 layers of phospholipids • Phosphate head is polar (water loving) Phospholipid • Fatty acid tails non-polar (water fearing) • Proteins embedded in membrane Lipid Bilayer @ 2011 Center for Pre-College Programs, New Jersey Institute of Technology, Newark, New Jersey Polar heads Fluid Mosaic love water Model of the & dissolve. cell membrane Non-polar tails hide from water. Carbohydrate cell markers Proteins @ 2011 Center for Pre-College Programs, New Jersey Institute of Technology, Newark, New Jersey 2 About Cell Membranes (continued) • 4. Cell membranes have pores (holes) in it • Selectively permeable: Allows some molecules in and keeps other molecules out • The structure helps it be selective! Pores @ 2011 Center for Pre-College Programs, New Jersey Institute of Technology, Newark, New Jersey Structure of the Cell Membrane Outside of cell Carbohydrate Proteins chains Lipid Bilayer Transport Protein Phospholipids Inside of cell (cytoplasm) @ 2011 Center for Pre-College Programs, New Jersey Institute of Technology, Newark, New Jersey 3 Types of Cellular Transport • Passive Transport celldoesn’tuseenergy 1. Diffusion 2. Facilitated Diffusion 3. Osmosis • Active Transport cell does use energy 1. -
The Concise Guide to Pharmacology 2019/20
Edinburgh Research Explorer THE CONCISE GUIDE TO PHARMACOLOGY 2019/20 Citation for published version: Cgtp Collaborators 2019, 'THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Transporters', British Journal of Pharmacology, vol. 176 Suppl 1, pp. S397-S493. https://doi.org/10.1111/bph.14753 Digital Object Identifier (DOI): 10.1111/bph.14753 Link: Link to publication record in Edinburgh Research Explorer Document Version: Publisher's PDF, also known as Version of record Published In: British Journal of Pharmacology General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 28. Sep. 2021 S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Transporters. British Journal of Pharmacology (2019) 176, S397–S493 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Transporters Stephen PH Alexander1 , Eamonn Kelly2, Alistair Mathie3 ,JohnAPeters4 , Emma L Veale3 , Jane F Armstrong5 , Elena Faccenda5 ,SimonDHarding5 ,AdamJPawson5 , Joanna L -
Effect of Hydrolyzable Tannins on Glucose-Transporter Expression and Their Bioavailability in Pig Small-Intestinal 3D Cell Model
molecules Article Effect of Hydrolyzable Tannins on Glucose-Transporter Expression and Their Bioavailability in Pig Small-Intestinal 3D Cell Model Maksimiljan Brus 1 , Robert Frangež 2, Mario Gorenjak 3 , Petra Kotnik 4,5, Željko Knez 4,5 and Dejan Škorjanc 1,* 1 Faculty of Agriculture and Life Sciences, University of Maribor, Pivola 10, 2311 Hoˇce,Slovenia; [email protected] 2 Veterinary Faculty, Institute of Preclinical Sciences, University of Ljubljana, Gerbiˇceva60, 1000 Ljubljana, Slovenia; [email protected] 3 Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Taborska 8, 2000 Maribor, Slovenia; [email protected] 4 Department of Chemistry, Faculty of Medicine, University of Maribor, Taborska 8, 2000 Maribor, Slovenia; [email protected] (P.K.); [email protected] (Ž.K.) 5 Laboratory for Separation Processes and Product Design, Faculty of Chemistry and Chemical Engineering, University of Maribor, Smetanova 17, 2000 Maribor, Slovenia * Correspondence: [email protected]; Tel.: +386-2-320-90-25 Abstract: Intestinal transepithelial transport of glucose is mediated by glucose transporters, and affects postprandial blood-glucose levels. This study investigates the effect of wood extracts rich in hydrolyzable tannins (HTs) that originated from sweet chestnut (Castanea sativa Mill.) and oak (Quercus petraea) on the expression of glucose transporter genes and the uptake of glucose and HT constituents in a 3D porcine-small-intestine epithelial-cell model. The viability of epithelial cells CLAB and PSI exposed to different HTs was determined using alamarBlue®. qPCR was used to analyze the gene expression of SGLT1, GLUT2, GLUT4, and POLR2A. Glucose uptake was confirmed Citation: Brus, M.; Frangež, R.; by assay, and LC–MS/ MS was used for the analysis of HT bioavailability. -
Slc1a3-2A-Creert2 Mice Reveal Unique Features of Bergmann Glia and Augment a Growing Collection of Cre Drivers and Effectors In
www.nature.com/scientificreports OPEN Slc1a3‑2A‑CreERT2 mice reveal unique features of Bergmann glia and augment a growing collection of Cre drivers and efectors in the 129S4 genetic background Lech Kaczmarczyk1,2, Nicole Reichenbach2, Nelli Blank2, Maria Jonson1, Lars Dittrich2, Gabor C. Petzold2,3 & Walker S. Jackson1,2* Genetic variation is a primary determinant of phenotypic diversity. In laboratory mice, genetic variation can be a serious experimental confounder, and thus minimized through inbreeding. However, generalizations of results obtained with inbred strains must be made with caution, especially when working with complex phenotypes and disease models. Here we compared behavioral characteristics of C57Bl/6—the strain most widely used in biomedical research—with those of 129S4. In contrast to 129S4, C57Bl/6 demonstrated high within‑strain and intra‑litter behavioral hyperactivity. Although high consistency would be advantageous, the majority of disease models and transgenic tools are in C57Bl/6. We recently established six Cre driver lines and two Cre efector lines in 129S4. To augment this collection, we genetically engineered a Cre line to study astrocytes in 129S4. It was validated with two Cre efector lines: calcium indicator gCaMP5g‑tdTomato and RiboTag—a tool widely used to study cell type‑specifc translatomes. These reporters are in diferent genomic loci, and in both the Cre was functional and astrocyte‑specifc. We found that calcium signals lasted longer and had a higher amplitude in cortical compared to hippocampal astrocytes, genes linked to a single neurodegenerative disease have highly divergent expression patterns, and that ribosome proteins are non‑uniformly expressed across brain regions and cell types. -
Transport of Sugars
BI84CH32-Frommer ARI 29 April 2015 12:34 Transport of Sugars Li-Qing Chen,1,∗ Lily S. Cheung,1,∗ Liang Feng,3 Widmar Tanner,2 and Wolf B. Frommer1 1Department of Plant Biology, Carnegie Institution for Science, Stanford, California 94305; email: [email protected] 2Zellbiologie und Pflanzenbiochemie, Universitat¨ Regensburg, 93040 Regensburg, Germany 3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305 Annu. Rev. Biochem. 2015. 84:865–94 Keywords First published online as a Review in Advance on glucose, sucrose, carrier, GLUT, SGLT, SWEET March 5, 2015 The Annual Review of Biochemistry is online at Abstract biochem.annualreviews.org Soluble sugars serve five main purposes in multicellular organisms: as sources This article’s doi: of carbon skeletons, osmolytes, signals, and transient energy storage and as 10.1146/annurev-biochem-060614-033904 transport molecules. Most sugars are derived from photosynthetic organ- Copyright c 2015 by Annual Reviews. isms, particularly plants. In multicellular organisms, some cells specialize All rights reserved in providing sugars to other cells (e.g., intestinal and liver cells in animals, ∗ These authors contributed equally to this review. photosynthetic cells in plants), whereas others depend completely on an ex- Annu. Rev. Biochem. 2015.84:865-894. Downloaded from www.annualreviews.org ternal supply (e.g., brain cells, roots and seeds). This cellular exchange of Access provided by b-on: Universidade de Lisboa (UL) on 09/05/16. For personal use only. sugars requires transport proteins to mediate uptake or release from cells or subcellular compartments. Thus, not surprisingly, sugar transport is criti- cal for plants, animals, and humans.