In Vivo Formation of N-Nitroso Compounds and Detection of Their Mutagenic Activity in the Host-Mediated Assay1
Total Page:16
File Type:pdf, Size:1020Kb

Load more
Recommended publications
-
Nitroso and Nitro Compounds 11/22/2014 Part 1
Hai Dao Baran Group Meeting Nitroso and Nitro Compounds 11/22/2014 Part 1. Introduction Nitro Compounds O D(Kcal/mol) d (Å) NO NO+ Ph NO Ph N cellular signaling 2 N O N O OH CH3−NO 40 1.48 molecule in mammals a nitro compound a nitronic acid nitric oxide b.p = 100 oC (8 mm) o CH3−NO2 57 1.47 nitrosonium m.p = 84 C ion (pKa = 2−6) CH3−NH2 79 1.47 IR: υ(N=O): 1621-1539 cm-1 CH3−I 56 Nitro group is an EWG (both −I and −M) Reaction Modes Nitro group is a "sink" of electron Nitroso vs. olefin: e Diels-Alder reaction: as dienophiles Nu O NO − NO Ene reaction 3 2 2 NO + N R h 2 O e Cope rearrangement υ O O Nu R2 N N N R1 N Nitroso vs. carbonyl R1 O O O O O N O O hυ Nucleophilic addition [O] N R2 R O O R3 Other reaction modes nitrite Radical addition high temp low temp nitrolium EWG [H] ion brown color less ion Redox reaction Photochemical reaction Nitroso Compounds (C-Nitroso Compounds) R2 R1 O R3 R1 Synthesis of C-Nitroso Compounds 2 O R1 R 2 N R3 3 R 3 N R N R N 3 + R2 2 R N O With NO sources: NaNO2/HCl, NOBF4, NOCl, NOSbF6, RONO... 1 R O R R1 O Substitution trans-dimer monomer: blue color cis-dimer colorless colorless R R NOBF OH 4 - R = OH, OMe, Me, NR2, NHR N R2 R3 = H or NaNO /HCl - para-selectivity ΔG = 10 Kcal mol-1 Me 2 Me R1 NO oxime R rate determining step Blue color: n π∗ absorption band 630-790 nm IR: υ(N=O): 1621-1539 cm-1, dimer υ(N−O): 1300 (cis), 1200 (trans) cm-1 + 1 Me H NMR (α-C-H) δ = 4 ppm: nitroso is an EWG ON H 3 Kochi et al. -
ATSDR Case Studies in Environmental Medicine Nitrate/Nitrite Toxicity
ATSDR Case Studies in Environmental Medicine Nitrate/Nitrite Toxicity Agency for Toxic Substances and Disease Registry Case Studies in Environmental Medicine (CSEM) Nitrate/Nitrite Toxicity Course: WB2342 CE Original Date: December 5, 2013 CE Expiration Date: December 5, 2015 Key • Nitrate toxicity is a preventable cause of Concepts methemoglobinemia. • Infants younger than 4 months of age are at particular risk of nitrate toxicity from contaminated well water. • The widespread use of nitrate fertilizers increases the risk of well-water contamination in rural areas. About This This educational case study document is one in a series of and Other self-instructional modules designed to increase the primary Case Studies care provider’s knowledge of hazardous substances in the in environment and to promote the adoption of medical Environmen- practices that aid in the evaluation and care of potentially tal Medicine exposed patients. The complete series of Case Studies in Environmental Medicine is located on the ATSDR Web site at URL: http://www.atsdr.cdc.gov/csem/csem.html In addition, the downloadable PDF version of this educational series and other environmental medicine materials provides content in an electronic, printable format. Acknowledgements We gratefully acknowledge the work of the medical writers, editors, and reviewers in producing this educational resource. Contributors to this version of the Case Study in Environmental Medicine are listed below. Please Note: Each content expert for this case study has indicated that there is no conflict of interest that would bias the case study content. CDC/ATSDR Author(s): Kim Gehle MD, MPH CDC/ATSDR Planners: Charlton Coles, Ph.D.; Kimberly Gehle, MD; Sharon L. -
Current Advances of Nitric Oxide in Cancer and Anticancer Therapeutics
Review Current Advances of Nitric Oxide in Cancer and Anticancer Therapeutics Joel Mintz 1,†, Anastasia Vedenko 2,†, Omar Rosete 3 , Khushi Shah 4, Gabriella Goldstein 5 , Joshua M. Hare 2,6,7 , Ranjith Ramasamy 3,6,* and Himanshu Arora 2,3,6,* 1 Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Davie, FL 33328, USA; [email protected] 2 John P Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; [email protected] (A.V.); [email protected] (J.M.H.) 3 Department of Urology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; [email protected] 4 College of Arts and Sciences, University of Miami, Miami, FL 33146, USA; [email protected] 5 College of Health Professions and Sciences, University of Central Florida, Orlando, FL 32816, USA; [email protected] 6 The Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA 7 Department of Medicine, Cardiology Division, Miller School of Medicine, University of Miami, Miami, FL 33136, USA * Correspondence: [email protected] (R.R.); [email protected] (H.A.) † These authors contributed equally to this work. Abstract: Nitric oxide (NO) is a short-lived, ubiquitous signaling molecule that affects numerous critical functions in the body. There are markedly conflicting findings in the literature regarding the bimodal effects of NO in carcinogenesis and tumor progression, which has important consequences for treatment. Several preclinical and clinical studies have suggested that both pro- and antitumori- Citation: Mintz, J.; Vedenko, A.; genic effects of NO depend on multiple aspects, including, but not limited to, tissue of generation, the Rosete, O.; Shah, K.; Goldstein, G.; level of production, the oxidative/reductive (redox) environment in which this radical is generated, Hare, J.M; Ramasamy, R.; Arora, H. -
Mechanisms of Nitric Oxide Reactions Mediated by Biologically Relevant Metal Centers
Struct Bond (2014) 154: 99–136 DOI: 10.1007/430_2013_117 # Springer-Verlag Berlin Heidelberg 2013 Published online: 5 October 2013 Mechanisms of Nitric Oxide Reactions Mediated by Biologically Relevant Metal Centers Peter C. Ford, Jose Clayston Melo Pereira, and Katrina M. Miranda Abstract Here, we present an overview of mechanisms relevant to the formation and several key reactions of nitric oxide (nitrogen monoxide) complexes with biologically relevant metal centers. The focus will be largely on iron and copper complexes. We will discuss the applications of both thermal and photochemical methodologies for investigating such reactions quantitatively. Keywords Copper Á Heme models Á Hemes Á Iron Á Metalloproteins Á Nitric oxide Contents 1 Introduction .................................................................................. 101 2 Metal-Nitrosyl Bonding ..................................................................... 101 3 How Does the Coordinated Nitrosyl Affect the Metal Center? .. .. .. .. .. .. .. .. .. .. .. 104 4 The Formation and Decay of Metal Nitrosyls ............................................. 107 4.1 Some General Considerations ........................................................ 107 4.2 Rates of NO Reactions with Hemes and Heme Models ............................. 110 4.3 Mechanistic Studies of NO “On” and “Off” Reactions with Hemes and Heme Models ................................................................................. 115 4.4 Non-Heme Iron Complexes .......................................................... -
Nitrosamines EMEA-H-A5(3)-1490
25 June 2020 EMA/369136/2020 Committee for Medicinal Products for Human Use (CHMP) Assessment report Procedure under Article 5(3) of Regulation EC (No) 726/2004 Nitrosamine impurities in human medicinal products Procedure number: EMEA/H/A-5(3)/1490 Note: Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2020. Reproduction is authorised provided the source is acknowledged. Table of contents Table of contents ...................................................................................... 2 1. Information on the procedure ............................................................... 7 2. Scientific discussion .............................................................................. 7 2.1. Introduction......................................................................................................... 7 2.2. Quality and safety aspects ..................................................................................... 7 2.2.1. Root causes for presence of N-nitrosamines in medicinal products and measures to mitigate them............................................................................................................. 8 2.2.2. Presence and formation of N-nitrosamines -
A Nitric Oxide/Cysteine Interaction Mediates the Activation of Soluble Guanylate Cyclase
A nitric oxide/cysteine interaction mediates the activation of soluble guanylate cyclase Nathaniel B. Fernhoffa,1, Emily R. Derbyshirea,1,2, and Michael A. Marlettaa,b,c,3 Departments of aMolecular and Cell Biology and bChemistry, University of California, Berkeley, CA 94720; and cCalifornia Institute for Quantitative Biosciences and Division of Physical Biosciences, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 Contributed by Michael A. Marletta, October 1, 2009 (sent for review August 22, 2009) Nitric oxide (NO) regulates a number of essential physiological pro- high activity of the xsNO state rapidly reverts to the low activity of cesses by activating soluble guanylate cyclase (sGC) to produce the the 1-NO state. Thus, all three sGC states (basal, 1-NO, and xsNO) second messenger cGMP. The mechanism of NO sensing was previ- can be prepared and studied in vitro (7, 8). Importantly, these ously thought to result exclusively from NO binding to the sGC heme; results define two different states of purified sGC with heme bound however, recent studies indicate that heme-bound NO only partially NO (7, 8), one with a high activity and one with a low activity. activates sGC and additional NO is involved in the mechanism of Further evidence for a non-heme NO binding site was obtained maximal NO activation. Furthermore, thiol oxidation of sGC cysteines by blocking the heme site with the tight-binding ligand butyl results in the loss of enzyme activity. Herein the role of cysteines in isocyanide, and then showing that NO still activated the enzyme NO-stimulated sGC activity investigated. We find that the thiol mod- (14). -
Systems Biology Reveals Reprogramming of the S-Nitroso
www.nature.com/scientificreports OPEN Systems biology reveals reprogramming of the S‑nitroso‑proteome in the cortical and striatal regions of mice during aging process Maryam Kartawy, Igor Khaliulin & Haitham Amal* Cell aging depends on the rate of cumulative oxidative and nitrosative damage to DNA and proteins. Accumulated data indicate the involvement of protein S‑nitrosylation (SNO), the nitric oxide (NO)-mediated posttranslational modifcation (PTM) of cysteine thiols, in diferent brain disorders. However, the changes and involvement of SNO in aging including the development of the organism from juvenile to adult state is still unknown. In this study, using the state‑of‑the‑ art mass spectrometry technology to identify S‑nitrosylated proteins combined with large‑scale computational biology, we tested the S‑nitroso‑proteome in juvenile and adult mice in both cortical and striatal regions. We found reprogramming of the S‑nitroso‑proteome in adult mice of both cortex and striatum regions. Signifcant biological processes and protein–protein clusters associated with synaptic and neuronal terms were enriched in adult mice. Extensive quantitative analysis revealed a large set of potentially pathological proteins that were signifcantly upregulated in adult mice. Our approach, combined with large scale computational biology allowed us to perform a system‑level characterization and identifcation of the key proteins and biological processes that can serve as drug targets for aging and brain disorders in future studies. Nitric oxide (NO) is produced in diferent organs and tissues, including the central and peripheral nervous sys- tem, and is one of the most important signaling molecules in the body1,2. At low concentrations, it participates in cell signaling and may have therapeutic value for brain injury 3. -
Accelerating Effect of Ascorbic Acid on A/-Nitrosamine Formation and Nitrosation by Oxyhyponitrite1
[CANCER RESEARCH 39, 3871-3874, October 1979] 0008-5472/79/0039-OOOOS02.00 Accelerating Effect of Ascorbic Acid on A/-Nitrosamine Formation and Nitrosation by Oxyhyponitrite1 Shaw-Kong Chang,2 George W. Harrington,5 Marc Rothstein,3 William A. Shergalis,4 Daniel Swern, and Saroj K. Vohra. Department of Chemistry, Temple University. Philadelphia. Pennsylvania 19122, and the Fels Research Institute. Temple University, Philadelphia. Pennsylvania 19140 ABSTRACT ments to be made readily during the initial and intermediate stages of reaction. DPP as used in this study avoids this The reaction of nitrite ion with ascorbic acid and its effect on difficulty and allows reactions to be studied in situ, yielding the rate of nitrosation of secondary amines have been investi interesting results. The use of DPP as an analytical method for gated by differential pulse polarography in aqueous acidic A/-nitrosamines and as a technique to study some of the chem solution. Ascorbic acid shows nonuniform behavior: it accel istry of W-nitrosamines has been previously reported by us (6- erates the nitrosation of N-methylaniline between pH 1.00 and 8, 31, 32). 1.95, allows the nitrosation of diphenylamine and iminodiace- tonitrile, but inhibits the nitrosation of secondary amines, such MATERIALS AND METHODS as dimethylamine, diethylamine, proline, hydroxyproline, N- methylaminoacetonitrile, N-methylaminopropionitrile, and sar- Instrumentation. The instrumentation, cells, and conditions cosine. The nitrosating agent generated by the reaction be used for DPP and spectral studies have been previously de tween ascorbic acid and nitrite ion appears to be oxyhyponitrite scribed (6, 7). The pH was measured with a Leeds & Northrup ion (N2CV2). -
C-Nitroso-Substituted Ligands of Poly(ADP-Ribose) Polymerase (Zinc Rmger/Drug-Induced Cell Death) WILLIAM G
Proc. Nati. Acad. Sci. USA Vol. 89, pp. 7703-7707, August 1992 Pharmacology Induction of endonuclease-mediated apoptosis in tumor cells by C-nitroso-substituted ligands of poly(ADP-ribose) polymerase (zinc rmger/drug-induced cell death) WILLIAM G. RICE*t, CHRISTOPHER D. HILLYERt, BRAD HARTEN*, CATHERINE A. SCHAEFFER*, MARK DORMINY*, DIXON A. LACKEY III*, EVA KIRSTEN§, JEROME MENDELEYEV§, KALMAN G. BUKI§, ALAEDDIN HAKAM§, AND ERNEST KUNt§ *Division of Hematology and Oncology, Department of Pediatrics, and tDepartment of Pathology and Laboratory of Medicine and the Winship Cancer Center, Emory University School of Medicine, Atlanta, GA 30322; and §Laboratory for Environmental Toxicology and Chemistry, The Romberg Tiburon Center, San Francisco State University, P.O. Box 855, Tiburon, CA 94920 Communicated by John Baldeschwieler, May 19, 1992 ABSTRACT 6-Nitroso-1,2-benzopyrone and 3-ni- Assays. For cell proliferation tests, cells were cultured in trosobenzamide, two C-nitroso compounds that inactivate the 96-well tissue culture plates at 3 x 103 cells per well (250-gl eukaryotic nuclear protein poly(ADP-ribose) polymerase total volume per well) for 2 hr (or the indicated length oftime) [NAD+:poly(adenosine diphosphate D-ribose) ADP-D-ribosyl- in the absence or presence of various concentrations of transferase, ADPRT, EC 2.4.2.30] at one zinc-ringer site, NOBA or NOBP; thereafter 0.5 ,uCi of [methyl-3H]thymidine completely suppressed the proliferation of leukemic and other (85 Ci/mmol; 1 Ci = 37 GBq) was added per well and its malignant human cells and subsequently produced cell death. incorporation into DNA following an 18-hr incubation was Tumoricidal concentrations of the drugs were relatively harm- determined radiochemically (6). -
Does N-Nitrosomelatonin Compete with S-Nitrosothiols As a Long
nalytic A al & B y i tr o Singh et al., Biochem Anal Biochem 2016, 5:1 s c i h e m m Biochemistry & e DOI: 10.4172/2161-1009.1000262 i h s c t r o i y B ISSN: 2161-1009 Analytical Biochemistry Commentary Open Access Does N-Nitrosomelatonin Compete with S-Nitrosothiols as a Long Distance Nitric Oxide Carrier in Plants? Neha Singh, Harmeet Kaur, Sunita Yadav and Satich C Bhatla* Laboratory of Plant Physiology and Biochemistry, Department of Botany, University of Delhi, India Plants transmit a variety of signaling molecules from roots to of proteins [13]. aerial parts, and vice-versa, in response to their growth conditions Determination of GSNO in plant samples still presents a (environment, nutrients, stress factors etc.). A signaling molecule challenge due to several technical obstacles and cumbersome sample should be produced quickly, induce a defined effect within the cell preparation procedures. It can also be affected by light, metal-catalyzed and be removed or metabolized rapidly when not required. Nitric SNO decomposition, enzymatic degradation catalyzed by GSNO oxide (NO) plays significant signaling roles in plant cells since it has reductase, and a reduction in the S-NO bond caused by reductants and all the above-stated features. It is a gaseous free radical, can gain or endogenous thiols [13]. Two different approaches to detect GSNO have lose an electron, has short half-life ( ̴ 30 sec) and it can exist in three been reported in higher plants: immunohistochemical analysis using interchangeable forms, namely the radical (NO•), the nitrosonium commercial antibodies against GSNO and liquid chromatography- cation (NO+) and as nitroxyl radical (NO). -
II.1.8 Alkyl Nitrites by Yasuo Seto
1.8 II.1.8 Alkyl nitrites by Yasuo Seto Introduction Alkyl nitrites are highly volatile organic solvents of aliphatic alcohol esters of nitrites [1]. Amyl nitritea, butyl nitrite and isobutyl nitrite are the representative alkyl nitrites; their boiling points are 98, 78 and 67 °C, respectively. Amyl nitrite is being widely used as a detoxicant for cyanide poisoning, because alkyl nitrites oxidize hemoglobin in erythrocytes to yield methemogloblin, which is bound with cyanide to inactivate it [1]. Alkyl nitrites also show a coronary artery-di- lating eff ect, and had been, therefore, used for the treatment of angina pectoris many years ago [2]; the pharmacological eff ect of the dilation of the coronary arteries was found due to the action of nitrogen monoxide produced by decomposition of alkyl nitrites [3]. Th ey are being mainly used as materials for manufacturing drugs or as reagents for synthesis in industries; they are also used as aromatics. Because of their pharmacological eff ect, alkyl nitrites are being abused as uncontrolled inhalant drugs and causing a social problem [4]. Although there are many reports on toxic and fatal cases due to alkyl nitrites [5], reports on their fatal doses are few; it is estimated that oral ingestion of 10–15 mL of each alkyl nitrite causes serious methe- moglobinemia [6]. Th e LD50 value for an alkyl nitrite is reported to be 205 mg/kg. Th ere are not many cases of analysis of alkyl nitrites in the fi eld of forensic toxicology. In this chapter, the methods for analysis of the compounds by headspace (HS)-gas chromatography (GC) and liquid-liquid extraction-GC are presented. -
Regulation of Protein Function by S-Nitrosation and S-Glutathionylation: Processes and Targets in Cardiovascular Pathophysiology
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Archivio della Ricerca - Università di Pisa Biol. Chem. 2017; 398(12): 1267–1293 Review Eugenia Belcastro, Caroline Gaucher, Alessandro Corti, Pierre Leroy, Isabelle Lartaud and Alfonso Pompella* Regulation of protein function by S-nitrosation and S-glutathionylation: processes and targets in cardiovascular pathophysiology https://doi.org/10.1515/hsz-2017-0150 aims to provide an update of available knowledge in the Received April 26, 2017; accepted August 7, 2017; previously field, with a special focus on the respective (sometimes published online August 19, 2017 competing and antagonistic) roles played by protein S-nitrosations and S-thionylations in biochemical and cel- Abstract: Decades of chemical, biochemical and patho- lular processes specifically pertaining to pathogenesis of physiological research have established the relevance cardiovascular diseases. of post-translational protein modifications induced by processes related to oxidative stress, with critical reflec- Keywords: cardiovascular diseases; glutathione; mixed tions on cellular signal transduction pathways. A great disulfides; nitric oxide; RNS; ROS; S-glutathionylation; deal of the so-called ‘redox regulation’ of cell function is S-nitrosation. in fact mediated through reactions promoted by reactive oxygen and nitrogen species on more or less specific ami- noacid residues in proteins, at various levels within the cell machinery. Modifications involving cysteine residues Introduction have received most attention, due to the critical roles they The role of nitric oxide (NO) in several signaling routes play in determining the structure/function correlates in has been clearly established (Grisham et al., 1999; Pacher proteins. The peculiar reactivity of these residues results et al., 2007).