Towards the Elucidation of Orphan Lysosomal Transporters Quentin Verdon
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Supplementary Materials
1 Supplementary Materials: Supplemental Figure 1. Gene expression profiles of kidneys in the Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice. (A) A heat map of microarray data show the genes that significantly changed up to 2 fold compared between Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice (N=4 mice per group; p<0.05). Data show in log2 (sample/wild-type). 2 Supplemental Figure 2. Sting signaling is essential for immuno-phenotypes of the Fcgr2b-/-lupus mice. (A-C) Flow cytometry analysis of splenocytes isolated from wild-type, Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice at the age of 6-7 months (N= 13-14 per group). Data shown in the percentage of (A) CD4+ ICOS+ cells, (B) B220+ I-Ab+ cells and (C) CD138+ cells. Data show as mean ± SEM (*p < 0.05, **p<0.01 and ***p<0.001). 3 Supplemental Figure 3. Phenotypes of Sting activated dendritic cells. (A) Representative of western blot analysis from immunoprecipitation with Sting of Fcgr2b-/- mice (N= 4). The band was shown in STING protein of activated BMDC with DMXAA at 0, 3 and 6 hr. and phosphorylation of STING at Ser357. (B) Mass spectra of phosphorylation of STING at Ser357 of activated BMDC from Fcgr2b-/- mice after stimulated with DMXAA for 3 hour and followed by immunoprecipitation with STING. (C) Sting-activated BMDC were co-cultured with LYN inhibitor PP2 and analyzed by flow cytometry, which showed the mean fluorescence intensity (MFI) of IAb expressing DC (N = 3 mice per group). 4 Supplemental Table 1. Lists of up and down of regulated proteins Accession No. -
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 -
Biomarker Status of the Human Equilibrative Nucleoside
cancers Article “Open Sesame?”: Biomarker Status of the Human Equilibrative Nucleoside Transporter-1 and Molecular Mechanisms Influencing its Expression and Activity in the Uptake and Cytotoxicity of Gemcitabine in Pancreatic Cancer 1,2, 1, 1,3 1 Ornella Randazzo y, Filippo Papini y, Giulia Mantini , Alessandro Gregori , Barbara Parrino 2, Daniel S. K. Liu 4 , Stella Cascioferro 2 , Daniela Carbone 2 , 1,5 4,6, 1,7, Godefridus J. Peters , Adam E. Frampton * , Ingrid Garajova y and Elisa Giovannetti 1,3,* 1 Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center (VUmc), 1081 HV Amsterdam, The Netherlands; [email protected] (O.R.); [email protected] (F.P.); [email protected] (G.M.); [email protected] (A.G.); [email protected] (G.J.P.); [email protected] (I.G.) 2 Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, 90123 Palermo, Italy; [email protected] (B.P.); [email protected] (S.C.); [email protected] (D.C.) 3 Cancer Pharmacology Lab, AIRC Start Up Unit, Fondazione Pisana per la Scienza, 56017 Pisa, Italy 4 Division of Cancer, Department of Surgery & Cancer, Imperial College, Hammersmith Hospital campus, London W12 0NN, UK;; [email protected] 5 Department of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, Poland 6 Faculty of Health and Medical Sciences, The Leggett Building, University of Surrey, Guildford GU2 7XH, UK 7 Medical Oncology Unit, University Hospital of Parma, Via Gramsci 14, 43126 Parma, Italy * Correspondence: [email protected] (A.E.F.); [email protected] (E.G.); Tel.: +31-003-120-444-2633 (E.G.) These authors contributed equally to this paper. -
Toxicological Profile for Nitrate and Nitrite
NITRATE AND NITRITE 29 3. HEALTH EFFECTS 3.1 INTRODUCTION The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and other interested individuals and groups with an overall perspective on the toxicology of nitrate and nitrite. It contains descriptions and evaluations of toxicological studies and epidemiological investigations and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. A glossary and list of acronyms, abbreviations, and symbols can be found at the end of this profile. 3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE To help public health professionals and others address the needs of persons living or working near hazardous waste sites, the information in this section is organized first by route of exposure (inhalation, oral, and dermal) and then by health effect (e.g., death, systemic, immunological, neurological, reproductive, developmental, and carcinogenic effects). These data are discussed in terms of three exposure periods: acute (14 days or less), intermediate (15–364 days), and chronic (365 days or more). Levels of significant exposure for each route and duration are presented in tables and illustrated in figures. The points in the figures showing no-observed-adverse-effect levels (NOAELs) or lowest- observed-adverse-effect levels (LOAELs) reflect the actual doses (levels of exposure) used in the studies. LOAELs have been classified into "less serious" or "serious" effects. "Serious" effects are those that evoke failure in a biological system and can lead to morbidity or mortality (e.g., acute respiratory distress or death). "Less serious" effects are those that are not expected to cause significant dysfunction or death, or those whose significance to the organism is not entirely clear. -
Sialic Acid Storage Disease
Sialic acid storage disease Description Sialic acid storage disease is an inherited disorder that primarily affects the nervous system. People with sialic acid storage disease have signs and symptoms that may vary widely in severity. This disorder is generally classified into one of three forms: infantile free sialic acid storage disease, Salla disease, and intermediate severe Salla disease. Infantile free sialic acid storage disease (ISSD) is the most severe form of this disorder. Babies with this condition have severe developmental delay, weak muscle tone ( hypotonia), and failure to gain weight and grow at the expected rate (failure to thrive). They may have unusual facial features that are often described as "coarse," seizures, bone malformations, an enlarged liver and spleen (hepatosplenomegaly), and an enlarged heart (cardiomegaly). The abdomen may be swollen due to the enlarged organs and an abnormal buildup of fluid in the abdominal cavity (ascites). Affected infants may have a condition called hydrops fetalis in which excess fluid accumulates in the body before birth. Children with this severe form of the condition usually live only into early childhood. Salla disease is a less severe form of sialic acid storage disease. Babies with Salla disease usually begin exhibiting hypotonia during the first year of life and go on to experience progressive neurological problems. Signs and symptoms of Salla disease include intellectual disability and developmental delay, seizures, problems with movement and balance (ataxia), abnormal tensing of the muscles (spasticity), and involuntary slow, sinuous movements of the limbs (athetosis). Individuals with Salla disease usually survive into adulthood. People with intermediate severe Salla disease have signs and symptoms that fall between those of ISSD and Salla disease in severity. -
Sialin (SLC17A5) Functions As a Nitrate Transporter in the Plasma Membrane
Sialin (SLC17A5) functions as a nitrate transporter in the plasma membrane Lizheng Qina,1, Xibao Liub,1, Qifei Suna, Zhipeng Fana, Dengsheng Xiaa, Gang Dinga, Hwei Ling Ongb, David Adamsc, William A. Gahlc, Changyu Zhengb, Senrong Qia, Luyuan Jina, Chunmei Zhanga, Liankun Gud, Junqi Hee, Dajun Dengd,2, Indu S. Ambudkarb,2, and Songlin Wanga,e,2 aSalivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050, China; bMolecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892; cMedical Genetics Branch, National Human Genome Research Institute, Bethesda, MD 20892; dKey Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing 100142, China; and eDepartment of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medicine, Beijing 100069, China Edited by Mark Gladwin, University of Pittsburg Medical Center, Pittsburgh, PA and accepted by the Editorial Board June 5, 2012 (received for review October 13, 2011) In vivo recycling of nitrate (NO −) and nitrite (NO −) is an important Nitrate uptake into salivary glands represents the key initial step 3 2 − alternative pathway for the generation of nitric oxide (NO) and in NO clearance from the serum; however, the mechanism me- 3 − maintenance of systemic nitrate–nitrite–NO balance. More than diating transport of NO3 in salivary gland epithelial cells has not − − fl 25% of the circulating NO3 is actively removed and secreted by yet been established. In this study, we examined NO3 in ux in − + salivary glands. Oral commensal bacteria convert salivary NO3 to salivary gland cells. -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
Potential Roles of Nitrate and Nitrite in Nitric Oxide Metabolism in the Eye Ji Won Park1, Barbora Piknova1, Audrey Jenkins2, David Hellinga2, Leonard M
www.nature.com/scientificreports OPEN Potential roles of nitrate and nitrite in nitric oxide metabolism in the eye Ji Won Park1, Barbora Piknova1, Audrey Jenkins2, David Hellinga2, Leonard M. Parver3 & Alan N. Schechter1* Nitric oxide (NO) signaling has been studied in the eye, including in the pathophysiology of some eye diseases. While NO production by nitric oxide synthase (NOS) enzymes in the eye has been − characterized, the more recently described pathways of NO generation by nitrate ( NO3 ) and nitrite − (NO2 ) ions reduction has received much less attention. To elucidate the potential roles of these pathways, we analyzed nitrate and nitrite levels in components of the eye and lacrimal glands, primarily in porcine samples. Nitrate and nitrite levels were higher in cornea than in other eye parts, while lens contained the least amounts. Lacrimal glands exhibited much higher levels of both ions compared to other organs, such as liver and skeletal muscle, and even to salivary glands which are known to concentrate these ions. Western blotting showed expression of sialin, a known nitrate transporter, in the lacrimal glands and other eye components, and also xanthine oxidoreductase, a nitrate and nitrite reductase, in cornea and sclera. Cornea and sclera homogenates possessed a measurable amount of nitrate reduction activity. These results suggest that nitrate ions are concentrated in the lacrimal glands by sialin and can be secreted into eye components via tears and then reduced to nitrite and NO, thereby being an important source of NO in the eye. Te NO generation pathway from L-arginine by endogenous NOS enzymes under normoxic conditions has been central in identifying the physiological roles of NO in numerous biological processes1. -
Mucopolysaccharidosis Type IIIA, and a Child with One SGSH Mutation and One GNS Mutation Is a Carrier
Mucopolysaccharidosis type III What is mucopolysaccharidosis type III? Mucopolysaccharidosis type III is an inherited metabolic disease that affects the central nervous system. Individuals with mucopolysaccharidosis type III have defects in one of four different enzymes required for the breakdown of large sugars known as glycosaminoglycans or mucopolysaccharides.1 The four enzymes, sulfamidase, alpha-N- acetylglucosaminidase, N-acetyltransferase, and N-acetylglucosamine-6-sulfatase, are associated with mucopolysaccharidosis types IIIA, IIIB, IIIC, and IIID, respectively.2-5 The signs and symptoms of all subtypes of mucopolysaccharidosis type III are similar and due to the build-up of the large sugar molecular heparan sulfate within lysosomes in cells. Mucopolysaccharidosis type III belongs to a group of diseases called lysosomal storage disorders and is also known as Sanfilippo syndrome.6 What are the symptoms of mucopolysaccharidosis type III and what treatment is available? Symptoms of mucopolysaccharidosis type III vary in severity and age at onset and are progressive. Affected individuals typically show no symptoms at birth.6 Signs and symptoms are typically seen in early childhood and may include:7 • Developmental and speech delays • Progressive cognitive deterioration and behavioral problems • Sleep disturbances • Frequent infections • Cardiac valve disease • Umbilical or groin hernias • Mild hepatomegaly (enlarged liver) • Decline in motor skills • Hearing loss and vision problems • Skeletal problems, including hip dysplasia and -
Structure-Activity Relationship and Mechanistic Studies on The
University of Tennessee Health Science Center UTHSC Digital Commons Theses and Dissertations (ETD) College of Graduate Health Sciences 12-2008 Structure-Activity Relationship and Mechanistic Studies on the Chemopreventive Activity of Dipyridamole and Its Analogues Ja’Wanda Shavon Grant University of Tennessee Health Science Center Follow this and additional works at: https://dc.uthsc.edu/dissertations Part of the Pharmacy and Pharmaceutical Sciences Commons Recommended Citation Grant, Ja’Wanda Shavon , "Structure-Activity Relationship and Mechanistic Studies on the Chemopreventive Activity of Dipyridamole and Its Analogues" (2008). Theses and Dissertations (ETD). Paper 100. http://dx.doi.org/10.21007/ etd.cghs.2008.0114. This Dissertation is brought to you for free and open access by the College of Graduate Health Sciences at UTHSC Digital Commons. It has been accepted for inclusion in Theses and Dissertations (ETD) by an authorized administrator of UTHSC Digital Commons. For more information, please contact [email protected]. Structure-Activity Relationship and Mechanistic Studies on the Chemopreventive Activity of Dipyridamole and Its Analogues Document Type Dissertation Degree Name Doctor of Philosophy (PhD) Program Pharmaceutical Sciences Research Advisor John K. Buolamwini, Ph.D. Committee Richard E. Lee, Ph.D. Duane Miller, Ph.D. David Nelson, Ph.D. Jie Zheng, Ph.D. DOI 10.21007/etd.cghs.2008.0114 This dissertation is available at UTHSC Digital Commons: https://dc.uthsc.edu/dissertations/100 STRUCTURE-ACTIVITY RELATIONSHIP AND -
Nucleoside Transporter Expression and Function in Cultured Mouse Astrocytes
GLIA 52:25–35 (2005) Nucleoside Transporter Expression and Function in Cultured Mouse Astrocytes LIANG PENG,1 RONG HUANG,2 ALBERT C.H. YU,1 KING Y. FUNG,1 MICHEL P. RATHBONE,3 AND LEIF HERTZ1,2* 1Hong Kong DNA Chips, Ltd., Kowloon, Hong Kong, China 2Department of Pharmacology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada 3Department of Medicine, McMaster University, Hamilton, Ontario, Canada KEY WORDS and play important roles in energy homeostasis and sig- adenosine; CNT2; ENT1; ENT2; guanosine; thymidine naling; (3) astrocytes synthesize guanine nucleotides (Pelled et al., 1999); (4) ATP is released from astrocytes during the propagation of Ca21 waves (Guthrie et al., ABSTRACT 1999) and degraded extracellularly; and (5) adenosine Uptake of purine and pyrimidine nucleosides in astrocytes is and guanosine function as neuromodulators, acting on P1 important for several reasons: (1) uptake of nucleosides con- tributes to nucleic acid synthesis; (2) astrocytes synthesize purinergic receptors of different subtypes in neurons and/ AMP, ADP, and ATP from adenosine and GTP from guano- or astrocytes (van Calker and Hamprecht, 1979; Kim sine; and (3) adenosine and guanosine function as neuromo- et al., 1991; Rathbone et al., 1999; Ciccarelli et al., 2001; dulators, whose effects are partly terminated by cellular Chen et al., 2001; Di Iorio et al., 2004; Wittendorp et al., uptake. It has previously been shown that adenosine is 2004), and cellular uptake contributes to the termination rapidly accumulated by active uptake in astrocytes (Hertz of their neuromodulator effects. However, except for ade- and Matz, Neurochem Res 14:755–760, 1989), but the ratio nosine (Hertz, 1978; Thampy and Barnes, 1983; Bender between active uptake and metabolism-driven uptake of ade- and Hertz, 1986; Hosli€ and Hosli,€ 1988; Matz and Hertz, nosine is unknown, as are uptake characteristics for guano- 1990; Bender et al., 1994; Othman et al., 2002), only little sine. -
Human Induced Pluripotent Stem Cell–Derived Podocytes Mature Into Vascularized Glomeruli Upon Experimental Transplantation
BASIC RESEARCH www.jasn.org Human Induced Pluripotent Stem Cell–Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation † Sazia Sharmin,* Atsuhiro Taguchi,* Yusuke Kaku,* Yasuhiro Yoshimura,* Tomoko Ohmori,* ‡ † ‡ Tetsushi Sakuma, Masashi Mukoyama, Takashi Yamamoto, Hidetake Kurihara,§ and | Ryuichi Nishinakamura* *Department of Kidney Development, Institute of Molecular Embryology and Genetics, and †Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; ‡Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan; §Division of Anatomy, Juntendo University School of Medicine, Tokyo, Japan; and |Japan Science and Technology Agency, CREST, Kumamoto, Japan ABSTRACT Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in