DOCSLIB.ORG

Other Data Relevant to an Evaluation of Carcinogenicity and Its Mechanisms

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Other Data Relevant to an Evaluation of Carcinogenicity and Its Mechanisms 512 IARC MONOGRAPHS VOLUME 92 4. Other Data Relevant to an Evaluation of Carcinogenicity and its Mechanisms 4.1 Toxicokinetics 4.1.1 Absorption, distribution, metabolism and excretion (a) Overview This section provides an overview of the toxicokinetics of polycyclic aromatic hydrocarbons (PAHs). Other more comprehensive reviews of the toxicokinetics of PAHs include those by the Environmental Protection Agency (1991), the Agency for Toxic Substances and Disease Registry (ATSDR, 1995) and the International Programme on Chemical Safety (IPCS, 1998), as well as reviews on the metabolism and bioactivation of PAHs by Conney (1982), Cooper et al . (1983), Shaw and Connell (1994), Penning et al . (1999), Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2005) and Xue and Warshawsky (2005). Little is known about the toxicokinetics of mixtures of or individual PAHs in humans. Multiple studies have been conducted to monitor urinary metabolites of PAHs and PAH–DNA adducts in the lymphocytes of workers exposed to mixtures of PAHs. However, most of the available data on toxicokinetic parameters for PAHs derive from studies of benzo[ a]pyrene in animals. Because of their lipophilicity, PAHs dissolve into and are transported by diffusion across lipid/lipoprotein membranes of mammalian cells, thus facilitating their absorption by the respiratory tract, gastrointestinal tract and skin. PAHs with two or three rings can be absorbed more rapidly and extensively than those with five or six rings. Once absorbed, PAHs are widely distributed throughout the body, with some preferential distribution to or retention in fatty tissues. They are rapidly metabolized to more soluble metabolites (epoxides, phenols, dihydrodiols, phenol dihydrodiols, dihydrodiol epoxides, quinones and tetrols), and conjugates of these metabolites are formed with sulfate, glutathione (GSH) or glucuronic acid. The covalent binding of reactive PAH metabolites to form DNA adducts may represent a key molecular event in the formation of mutations and the initiation of cancer. The structures of the DNA adducts that are formed provide an inference of the precursor metabolites. PAHs are eliminated from the body principally as conjugated metabolites in the faeces, via biliary excretion, and in the urine. Most PAHs with potential biological activity range in size from two to six fused aromatic rings. Because of this vast range in molecular weight, several of the physicochemical properties that are critical to their biological activity vary greatly. Five properties in particular have a decisive influence on the biological activity of PAHs: their vapour pressure, their adsorption onto surfaces of solid carrier particles, their absorption into liquid carriers, their lipid/aqueous partition coefficient in tissues and their limits of solubility in the lipid and aqueous phases of tissues. POLYCYCLIC AROMATIC HYDROCARBONS 513 These properties are intrinsically linked with the metabolic activation of the most toxic PAHs, and an understanding of the nature of this interaction may facilitate the interpretation of studies on their deposition and disposition that are occasionally conflicting. Transporters may play a role in the biological activity of PAHs. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters (49 genes characterized in humans) transport specific molecules across lipid membranes including hydrophobic compounds and metabolites (Schinkel & Jonker, 2003). P-Glycoprotein transports mainly non-metabolized compounds and multidrug resistance-associated protein-1 (MRP1) and -2 conjugates of foreign compounds (Leslie et al. , 2001; Haimeur et al. , 2004). Several ABC transporters are polymorphic (Sakaeda et al. , 2004). Benzo[ a]pyrene conjugates may be substrates for ABC transporters, such as the GSH conjugate of benzo[ a]pyrene- 7,8-diol-9,10-oxide which is a substrate for MRP2 (Srivastava et al. , 2002) and benzo- [a]pyrene-3-glucuronide which is a substrate for breast cancer resistance protein (BCRP) (Ebert et al. , 2005). PAHs are ubiquitous in the environment due to volcanic eruptions and forest fires, and their presence in various media (i.e. air and soil) constitutes a background level of exposure. Additional exposure occurs through the ingestion of grilled or cured meats (see Section 1). These exposures should be taken into consideration when assessing health risks due to exposure to PAHs. (b) Absorption through the respiratory tract Vapour pressure is a major determinant for the distribution of a PAH between the particulate and gaseous phase of the aerosol by which the substance is emitted into the atmosphere. The vapour pressure of PAHs decreases drastically with increasing molecular weight (Lohmann & Lammel, 2004), so that two-ringed naphthalenes are mostly found in the gas phase whereas five-ringed PAHs such as benzo[ a]pyrene are mostly adsorbed on airborne particles at room temperature (Lane & Gundel, 1996). Strong sorption of a PAH onto particles can further increase the particle-bound fraction of that substance (Lohmann & Lammel, 2004). Because the most carcinogenic PAHs of greater size are, to a large degree, particle-associated, there is considerable potential for covariance with an inflammatory response that is induced by the carrier particles alone. Typical carbonaceous carrier particles of PAHs that have no adsorbed genotoxic material have been shown to be carcinogenic, particularly in rats (see IARC, 2010). This mechanism is, however, outside the scope of this monograph. Gas/particle partitioning is also of great importance during inhalation exposure in order to determine the probable sites of deposition within the respiratory tract. The smaller gaseous PAHs are deposited mostly as soluble vapours, whereas five- to six- ringed aromatic compounds are mostly particle-associated at ambient temperatures and can be expected to be deposited with the carrier particles. The rate and extent of absorption by the respiratory tract of PAHs from PAH-containing particles are dependent on particle size (i.e. aerodynamic diameter, which influences regional deposition in the respiratory tract) and the rate of release of PAHs from the particle. Because the release of PAHs from particles is extraneous in 514 IARC MONOGRAPHS VOLUME 92 exposure to vapours, the rate and extent of absorption of inhaled vapour-phase PAHs are different from those of particle-bound PAHs. After deposition in the respiratory tract, the sorptive properties of PAHs are a major determinant for the bioavailability of the substance in the organism. The timing of the release from carrier particles in particular affects the toxicity of inhaled PAHs at the site of entry. For solid particles, the major determinant for the release is the rate of desorption of the hydrocarbons from the surface, whereas for liquid aerosols, either the dissolution of the entire particle or desorption from insoluble carrier particles is a decisive factor. A rapid release from carrier particles gives a close correlation between the deposition pattern of inhaled aerosols and the site-of-entry exposures to particle-associated PAHs. Slower release alters the exposures, and shows a clearance pattern of inhaled particles. Substantial fractions of inhaled PAHs deposited in the tracheobronchial region and upper airways can be redistributed by the mucociliary escalator to the gastrointestinal tract, which thereby changes the exposure route from inhalation to ingestion (Sun et al ., 1982). Following deposition and desorption from their carrier particles, PAHs are absorbed through the epithelial barriers onto which they are deposited. The slow diffusion of highly lipophilic substances into the tissues is fundamental to the behaviour of PAHs in biological systems. This is a strictly physicochemical mechanism that needs to be considered in all measurements of the kinetics of PAHs in tissues. A highly lipophilic substance dissolves readily in the first lipid membrane it encounters, but is then transported slowly into the next layer (Gerde et al ., 1993a). This is due to the low concentration of lipophilic solute in the aqueous gaps between cell membranes, which results in a high concentration of solute in the epithelium at the site of entry, comparatively slow absorption into the circulation and a low concentration in all tissues distal to the site of entry. The absorption process is strongly dependent on the lipophilicity of the PAHs and their metabolites: with higher lipophilicities, the mobility of the substances by diffusion into tissues is lower and, with thicker entrance epithelium, the half-life of absorption into the capillary bed of the submucosa is longer. Highly lipophilic PAHs that are released from particles deposited in the conducting and bronchial airways are retained for several hours and absorbed slowly by a diffusion-limited process, whereas PAHs that are released from particles in alveolar airways are absorbed within minutes (Gerde et al ., 1991a,b; 1993a,b,c; Gerde & Scott, 2001). The relative thickness of the epithelium of the conducting airways compared with the thin epithelium of the alveolar region has been proposed as a contributing factor to this regional difference in duration of absorption following deposition. Slow absorption through the epithelium of the conduct- ing airways probably leads rapidly to saturation in the mucous lining layer and airway epithelium with increasing levels of exposure (Gerde et al. , 1991a,b). A probable consequence is an increase in the fraction of undissolved/undesorbed PAHs
Load more

Recommended publications
  • Contig Protein Description Symbol Anterior Posterior Ratio
    Table S2. List of proteins detected in anterior and posterior intestine pooled samples. Data on protein expression are mean ± SEM of 4 pools fed the experimental diets. The number of the contig in the Sea Bream Database (http://nutrigroup-iats.org/seabreamdb) is indicated. Contig Protein Description Symbol Anterior Posterior Ratio Ant/Pos C2_6629 1,4-alpha-glucan-branching enzyme GBE1 0.88±0.1 0.91±0.03 0.98 C2_4764 116 kDa U5 small nuclear ribonucleoprotein component EFTUD2 0.74±0.09 0.71±0.05 1.03 C2_299 14-3-3 protein beta/alpha-1 YWHAB 1.45±0.23 2.18±0.09 0.67 C2_268 14-3-3 protein epsilon YWHAE 1.28±0.2 2.01±0.13 0.63 C2_2474 14-3-3 protein gamma-1 YWHAG 1.8±0.41 2.72±0.09 0.66 C2_1017 14-3-3 protein zeta YWHAZ 1.33±0.14 4.41±0.38 0.30 C2_34474 14-3-3-like protein 2 YWHAQ 1.3±0.11 1.85±0.13 0.70 C2_4902 17-beta-hydroxysteroid dehydrogenase 14 HSD17B14 0.93±0.05 2.33±0.09 0.40 C2_3100 1-acylglycerol-3-phosphate O-acyltransferase ABHD5 ABHD5 0.85±0.07 0.78±0.13 1.10 C2_15440 1-phosphatidylinositol phosphodiesterase PLCD1 0.65±0.12 0.4±0.06 1.65 C2_12986 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase delta-1 PLCD1 0.76±0.08 1.15±0.16 0.66 C2_4412 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-2 PLCG2 1.13±0.08 2.08±0.27 0.54 C2_3170 2,4-dienoyl-CoA reductase, mitochondrial DECR1 1.16±0.1 0.83±0.03 1.39 C2_1520 26S protease regulatory subunit 10B PSMC6 1.37±0.21 1.43±0.04 0.96 C2_4264 26S protease regulatory subunit 4 PSMC1 1.2±0.2 1.78±0.08 0.68 C2_1666 26S protease regulatory subunit 6A PSMC3 1.44±0.24 1.61±0.08
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Independent Actions on Cyclin-Dependent Kinases and Aryl Hydrocarbon Receptor Mediate the Antiproliferative Effects of Indirubins
    Oncogene (2004) 23, 4400–4412 & 2004 Nature Publishing Group All rights reserved 0950-9232/04 $30.00 www.nature.com/onc Independent actions on cyclin-dependent kinases and aryl hydrocarbon receptor mediate the antiproliferative effects of indirubins Marie Knockaert1, Marc Blondel1, Ste´ phane Bach1, Maryse Leost1, Cem Elbi2, Gordon L Hager2, Scott RNagy 3, Dalho Han3, Michael Denison3, Martine Ffrench4, Xiaozhou P Ryan5, Prokopios Magiatis6, Panos Polychronopoulos6, Paul Greengard5, Leandros Skaltsounis6 and Laurent Meijer*,1,5 1C.N.R.S., Cell Cycle Group & UPS-2682, Station Biologique, BP 74, 29682 ROSCOFF cedex, Bretagne, France; 2Laboratory of Receptor Biology & Gene Expression, Bldg 41, Room B602, National Cancer Institute, NIH, Bethesda, MD 20892-5055, USA; 3Department of Environmental Toxicology, Meyer Hall, One Shields Avenue, University of California, Davis, CA 95616-8588, USA; 4Universite´ Claude Bernard, Laboratoire de Cytologie Analytique et Cytoge´ne´tique Mole´culaire, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France; 5Laboratory of Molecular & Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA; 6Division of Pharmacognosy and Natural Products Chemistry, Department of Pharmacy, University of Athens, Panepistimiopolis Zografou, GR-15771 Athens, Greece Indirubin, a bis-indole obtained from various natural Introduction sources, is responsible for the reported antileukemia activity of a Chinese Medicinal recipe, Danggui Longhui The bis-indole indirubin has been identified as the main Wan. However, its molecular mechanism of action is still active ingredient of a traditional Chinese medicinal not well understood. In addition to inhibition of cyclin- recipe, Danggui Longhui Wan, used to treat various dependent kinases and glycogen synthase kinase-3, diseases including chronic myelocytic leukemia (reviews indirubins have been reported to activate the aryl in Tang and Eisenbrand, 1992; Xiao et al., 2002).
    [Show full text]
  • Detection, Occurrence and Fate of Indirubin in Municipal Sewage
    Subscriber access provided by BEIJING UNIV Article Detection, Occurrence and Fate of Indirubin in Municipal Sewage Treatment Plants Jianying Hu, Hong Chang, Lezheng Wang, Shimin Wu, Bin Shao, Jun Zhou, and Ying Zhao Environ. Sci. Technol., 2008, 42 (22), 8339-8344• DOI: 10.1021/es801038y • Publication Date (Web): 11 October 2008 Downloaded from http://pubs.acs.org on March 12, 2009 More About This Article Additional resources and features associated with this article are available within the HTML version: • Supporting Information • Access to high resolution figures • Links to articles and content related to this article • Copyright permission to reproduce figures and/or text from this article Environmental Science & Technology is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Environ. Sci. Technol. 2008, 42, 8339–8344 to cause liver damage, growth retardation, certain types of Detection, Occurrence and Fate of cancer, birth defects, depression of immunological function, Indirubin in Municipal Sewage and reproductive problems in several species by binding to activating aryl hydrocarbon receptor (AhR) (3-6). These AhR Treatment Plants agonists have been identified in almost every component of the global ecosystem including fish, wildlife, human adipose tissue, milk, and serum (7). JIANYING HU,*,† HONG CHANG,† LEZHENG WANG,† SHIMIN WU,† Besides these chemicals, a wide variety of naturally BIN SHAO,‡ JUN ZHOU,§ AND occurring chemicals such as tetrapyroles, indoles, and YING ZHAO§ arachidonic acid metabolites have been also reported to be College of Urban and Environmental Science, Peking AhR agonists (8, 9). Some of these chemicals were reported University, Beijing 100871, China, Institute of Nutrition and to interact with AhR and produce activation or inhibition of Food Hygiene, Beijing Center for Disease Prevention and signal transduction.
    [Show full text]
  • Bilirubin and Beyond: a Review of Lipid Status in Gilbert's Syndrome and Its Relevance to Cardiovascular Disease Protection
    Bilirubin and beyond: A review of lipid status in Gilbert's syndrome and its relevance to cardiovascular disease protection Author Bulmer, AC, Verkade, HJ, Wagner, K-H Published 2013 Journal Title Progress in Lipid Research DOI https://doi.org/10.1016/j.plipres.2012.11.001 Copyright Statement © 2013 Elsevier. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version. Downloaded from http://hdl.handle.net/10072/54228 Griffith Research Online https://research-repository.griffith.edu.au Bilirubin and beyond: a review of lipid status in Gilbert’s syndrome and its relevance to cardiovascular disease protection Bulmer, A.C.1*, Verkade, H.J.2, Wagner, K-H3* 1Heart Foundation Research Centre, Griffith Health Institute, Griffith University, Gold Coast, Australia. 2Pediatric Gastroenterology – Hepatology, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, The Netherlands. 3Emerging Field Oxidative Stress and DNA Stability, Department of Nutritional Sciences, University of Vienna, Vienna, Austria. *Corresponding Authors Prof Karl-Heinz Wagner Department of Nutritional Sciences Althanstrasse 14, 1090, Vienna, Austria Ph: +43 1 427754930 Fax: +43 1 42779549 Dr Andrew Bulmer Heart Foundation Research Centre Griffith Health Institute Griffith University Parklands Avenue, Southport, Southport, 4222, Australia Ph: +61 7 55528215 Fax: +61 7 5552 8908 1 Abstract Gilbert’s syndrome (GS) is characterized by a benign, mildly elevated bilirubin concentration in the blood. Recent reports show clear protection from cardiovascular disease in this population. Protection of lipids, proteins and other macromolecules from oxidation by bilirubin represents the most commonly accepted mechanism contributing to protection in this group.
    [Show full text]
  • Investigation of the Underlying Hub Genes and Molexular Pathogensis in Gastric Cancer by Integrated Bioinformatic Analyses
    bioRxiv preprint doi: https://doi.org/10.1101/2020.12.20.423656; this version posted December 22, 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. Investigation of the underlying hub genes and molexular pathogensis in gastric cancer by integrated bioinformatic analyses Basavaraj Vastrad1, Chanabasayya Vastrad*2 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2020.12.20.423656; this version posted December 22, 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 The high mortality rate of gastric cancer (GC) is in part due to the absence of initial disclosure of its biomarkers. The recognition of important genes associated in GC is therefore recommended to advance clinical prognosis, diagnosis and and treatment outcomes. The current investigation used the microarray dataset GSE113255 RNA seq data from the Gene Expression Omnibus database to diagnose differentially expressed genes (DEGs). Pathway and gene ontology enrichment analyses were performed, and a proteinprotein interaction network, modules, target genes - miRNA regulatory network and target genes - TF regulatory network were constructed and analyzed. Finally, validation of hub genes was performed. The 1008 DEGs identified consisted of 505 up regulated genes and 503 down regulated genes.
    [Show full text]
  • Taylor Et Al REVISED MS28926-1.Pdf
    1 The effect of micronutrient supplementation on growth and hepatic 2 metabolism in diploid and triploid Atlantic salmon (Salmo salar) parr 3 fed a low marine ingredient diet 4 5 John F. Taylor a*, Luisa M. Vera a, Christian De Santis a, Erik-Jan Lock b, Marit Espe b, 6 Kaja H. Skjærven b, Daniel Leeming c, Jorge del Pozo d, Jose Mota-Velasco e, Herve 7 Migaud a, Kristin Hamre b, Douglas R. Tocher a 8 9 a Institute of Aquaculture, University of Stirling, Stirling, FK9 4LA, UK 10 b Institute of Marine Research, PO box 1870 Nordnes, 5817 Bergen, Norway 11 c BioMar Ltd., Grangemouth, FK3 8UL, UK 12 d The Royal (Dick) School of Veterinary Studies, Edinburgh, EH25 9RG, UK 13 e Hendrix Genetics, Landcatch Natural Selection Ltd., Lochgilphead, PA31 8PE, UK 14 15 Running Title: Dietary micronutrient supplementation in Atlantic salmon 16 17 ms. has 31 pg.s, 4 figures, 9 tables, 4 suppl. files 18 19 Corresponding Author: 20 Dr John F. Taylor 21 Institute of Aquaculture, University of Stirling, Stirling, FK9 4LA, UK 22 Tel: +44-01786 467929 ; Fax: +44-01768 472133 23 [email protected] 24 Accepted refereed manuscript of: Taylor JF, Vera LM, De Santis C, Lock E, Espe M, Skjaerven KH, Leeming D, Del Pozo J, Mota-Velasco J, Migaud H, Hamre K & Tocher DR (2019) The effect of micronutrient supplementation on growth and hepatic metabolism in diploid and triploid Atlantic salmon (Salmo salar) parr fed a low marine ingredient diet. Comparative Biochemistry and Physiology. Part B, Biochemistry and Molecular Biology, 227, pp.
    [Show full text]
  • Dioxin) Receptor
    TOXICOLOGICAL SCIENCES 124(1), 1–22 (2011) doi:10.1093/toxsci/kfr218 Advance Access publication September 9, 2011 Exactly the Same but Different: Promiscuity and Diversity in the Molecular Mechanisms of Action of the Aryl Hydrocarbon (Dioxin) Receptor Michael S. Denison,*,1 Anatoly A. Soshilov,* Guochun He,* Danica E. DeGroot,* and Bin Zhao† Downloaded from *Department of Environmental Toxicology, University of California, Davis, California 95616; and †Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China 1To whom correspondence should be addressed at Department of Environmental Toxicology, University of California, Meyer Hall, One Shields Avenue, Davis, CA 95616-8588. Fax: (530) 752-3394. E-mail: [email protected]. http://toxsci.oxfordjournals.org/ Received June 6, 2011; accepted August 12, 2011 toxic effects in a wide range of species and tissues (Beischlag The Ah receptor (AhR) is a ligand-dependent transcription et al., 2008; Furness and Whelan, 2009; Hankinson, 2005; factor that mediates a wide range of biological and toxicological Humblet et al., 2008; Marinkovic´ et al., 2010; Poland and effects that result from exposure to a structurally diverse variety Knutson, 1982; Safe, 1990; White and Birnbaum, 2009). The of synthetic and naturally occurring chemicals. Although the overall mechanism of action of the AhR has been extensively best-characterized high-affinity ligands for the AhR include at University of California, Davis - Library on May 4, 2012 studied and involves a classical nuclear receptor mechanism of a wide variety of ubiquitous hydrophobic environmental action (i.e., ligand-dependent nuclear localization, protein hetero- contaminants such as the halogenated aromatic hydrocarbons dimerization, binding of liganded receptor as a protein complex to (HAHs) and nonhalogenated polycyclic aromatic hydrocarbons its specific DNA recognition sequence and activation of gene (PAHs).
    [Show full text]
  • The Identification of Human Aldo-Keto Reductase AKR7A2 As a Novel
    Li et al. Cellular & Molecular Biology Letters (2016) 21:25 Cellular & Molecular DOI 10.1186/s11658-016-0026-9 Biology Letters SHORTCOMMUNICATION Open Access The identification of human aldo-keto reductase AKR7A2 as a novel cytoglobin- binding partner Xin Li, Shanshan Zou, Zhen Li, Gaotai Cai, Bohong Chen, Ping Wang and Wenqi Dong* * Correspondence: [email protected] Abstract Department of Biopharmaceutics, School of Laboratory Medicine and Cytoglobin (CYGB), a member of the globin family, is thought to protect cells from Biotechnology, Southern Medical reactive oxygen and nitrogen species and deal with hypoxic conditions and University, 1838 North Guangzhou oxidative stress. However, its molecular mechanisms of action are not clearly Avenue, Guangzhou 510515, China understood. Through immunoprecipitation combined with a two-dimensional electrophoresis–mass spectrometry assay, we identified a CYGB interactor: aldo-keto reductase family 7 member A2 (AKR7A2). The interaction was further confirmed using yeast two-hybrid and co-immunoprecipitation assays. Our results show that AKR7A2 physically interacts with CYGB. Keywords: CYGB, AKR7A2, Protein-protein interactions, Yeast two-hybrid assay, Co-immunoprecipitation, 2-DE, Oxidative stress Introduction Cytoglobin (CYGB), which is a member of the globin family, was discovered more than a decade ago in a proteomic screen of fibrotic liver [1]. It was originally named STAP (stellate activating protein). Human CYGB is a 190-amino acid, 21-kDa protein [2], encoded by a single copy gene mapped at the 17q25.3 chromosomal segment [3]. It has a compact helical conformation, giving it the ability to bind to heme, which allows reversible binding of gaseous, diatomic molecules, including oxygen (O2), nitric oxide (NO) and carbon monoxide (CO), just like hemoglobin (Hb), myoglobin (Mb) and neuroglobin (Ngb) [4].
    [Show full text]
  • Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
    Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement.
    [Show full text]
  • Supplementary Materials
    Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2003/0082511 A1 Brown Et Al
    US 20030082511A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2003/0082511 A1 Brown et al. (43) Pub. Date: May 1, 2003 (54) IDENTIFICATION OF MODULATORY Publication Classification MOLECULES USING INDUCIBLE PROMOTERS (51) Int. Cl." ............................... C12O 1/00; C12O 1/68 (52) U.S. Cl. ..................................................... 435/4; 435/6 (76) Inventors: Steven J. Brown, San Diego, CA (US); Damien J. Dunnington, San Diego, CA (US); Imran Clark, San Diego, CA (57) ABSTRACT (US) Correspondence Address: Methods for identifying an ion channel modulator, a target David B. Waller & Associates membrane receptor modulator molecule, and other modula 5677 Oberlin Drive tory molecules are disclosed, as well as cells and vectors for Suit 214 use in those methods. A polynucleotide encoding target is San Diego, CA 92121 (US) provided in a cell under control of an inducible promoter, and candidate modulatory molecules are contacted with the (21) Appl. No.: 09/965,201 cell after induction of the promoter to ascertain whether a change in a measurable physiological parameter occurs as a (22) Filed: Sep. 25, 2001 result of the candidate modulatory molecule. Patent Application Publication May 1, 2003 Sheet 1 of 8 US 2003/0082511 A1 KCNC1 cDNA F.G. 1 Patent Application Publication May 1, 2003 Sheet 2 of 8 US 2003/0082511 A1 49 - -9 G C EH H EH N t R M h so as se W M M MP N FIG.2 Patent Application Publication May 1, 2003 Sheet 3 of 8 US 2003/0082511 A1 FG. 3 Patent Application Publication May 1, 2003 Sheet 4 of 8 US 2003/0082511 A1 KCNC1 ITREXCHO KC 150 mM KC 2000000 so 100 mM induced Uninduced Steady state O 100 200 300 400 500 600 700 Time (seconds) FIG.
    [Show full text]