Identification of 4-S-Cysteinyltetrodotoxin from the liver of the puffer fish, Fugu pardalis, and formation of thiol adducts of tetrodotoxin from 4,9-anhydrotetrodotoxin.

Abstract:

:The metabolic pathway of tetrodotoxin (TTX), a powerful and specific voltage-gated sodium channel blocker, has not been well-clarified either in TTX-poisoned patients or in puffer fish. 4-S-CysteinylTTX (4-CysTTX) was isolated from the liver of the puffer fish, Fugu pardalis, as the first adduct of TTX with thiol. The structure was fully characterized by electrospray ionization-MS and two-dimensional NMR spectroscopy. The configuration of Cys in this compound was confirmed to be S (L-Cys) by application of the Marfey's method to cystine obtained from 4-CysTTX by iodine oxidation. We also found that 4-CysTTX was derived from 4,9-anhydroTTX by incubation with a large excess of Cys in aqueous buffer (pH 8.0) for 90 min at 40 degrees C in 33% yield by HPLC. GSH also reacted with 4,9-anhydroTTX to form 4-S-glutathionylTTX (4-GSTTX) in 39% yield under the same conditions, whereas TTX scarcely reacted with Cys and GSH. These reactions were strictly pH-dependent, giving the highest yield at pH 8.0. 4-GSTTX was converted to 4,9-anhydroTTX in 0.8 M sodium phosphate buffer (pH 8.0) at 25 degrees C. Its half-life was approximately 4 h. The minimum lethal doses of 4-CysTTX and 4-GSTTX to mice by ip injection were more than 140 and 860 microg/kg (n = 2), which were 14- and 86-fold larger than the LD(50) of TTX, respectively. 4-GSTTX was hydrolyzed to 4-CysTTX by gamma-glutamyltranspeptidase (Sigma, catalog no. G9270), which was supposed to contain cysteinylglycine dipeptidase. We also examined the effect of Cys or GSH coinjection (ip) with TTX to mice for detoxification of TTX and concluded that these coinjections did not reduce the toxicity of TTX.

journal_name

Chem Res Toxicol

authors

Yotsu-Yamashita M,Goto A,Nakagawa T

doi

10.1021/tx050015g

subject

Has Abstract

pub_date

2005-05-01 00:00:00

pages

865-71

issue

5

eissn

0893-228X

issn

1520-5010

journal_volume

18

pub_type

杂志文章
  • A comparison of the covalent binding of clozapine, procainamide, and vesnarinone to human neutrophils in vitro and rat tissues in vitro and in vivo.

    abstract::Covalent binding of drug reactive metabolites to neutrophils or their precursors is thought to play a role in the development of drug-induced agranulocytosis. In this study, we used immunochemical techniques to compare the covalent binding of clozapine, vesnarinone, and procainamide (three drugs associated with agranu...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx050095o

    authors: Gardner I,Popović M,Zahid N,Uetrecht JP

    更新日期:2005-09-01 00:00:00

  • Reactions of amino acids, peptides, and proteins with oxidized metabolites of tris(p-carboxyltetrathiaaryl)methyl radical EPR probes.

    abstract::Oxidation of the tris(p-carboxyltetrathiaaryl)methyl (TAM) EPR radical probe, TAMa(•), by rat liver microsomes (RLM) + NADPH, or horseradish peroxidase (HRP) + H2O2, or K2IrCl6, led to an intermediate cation, TAMa(+), which was treated with glutathione (GSH), with formation of an adduct, TAMa-SG(•), resulting from the...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx400467p

    authors: Decroos C,Boucher JL,Mansuy D,Xu-Li Y

    更新日期:2014-04-21 00:00:00

  • Modulation of the mitochondrial cytochrome bc1 complex activity by chromanols and related compounds.

    abstract::Tocopherols (alpha-, beta-, gamma-, and delta-Toc) and tocopheryl quinones (alpha-, beta-, gamma-, and delta-TQ) were recently suggested to modulate mitochondrial electron transfer in mammals. Intriguingly, Tocs and stigmatellin, a potent inhibitor of the mitochondrial cytochrome (cyt) bc(1) complex, possess a common ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx900333f

    authors: Müllebner A,Patel A,Stamberg W,Staniek K,Rosenau T,Netscher T,Gille L

    更新日期:2010-01-01 00:00:00

  • Nickel Oxide (NiO) Nanoparticles Induce Loss of Cell Viability in Yeast Mediated by Oxidative Stress.

    abstract::The present work aimed to elucidate whether the toxic effects of nickel oxide (NiO) nanoparticles (NPs) on the yeast Saccharomyces cerevisiae were associated with oxidative stress (OS) and what mechanisms may have contributed to this OS. Cells exposed to NiO NPs accumulated superoxide anions and hydrogen peroxide, whi...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.8b00022

    authors: Sousa CA,Soares HMVM,Soares EV

    更新日期:2018-08-20 00:00:00

  • Effects of the peroxisome proliferator perfluoro-n-decanoic acid on hepatic gluconeogenesis and glycogenesis: a 13C NMR investigation.

    abstract::Carbon-13 NMR spectroscopy was used to study the effects of the peroxisome proliferator perfluoro-n-decanoic acid (PFDA) on hepatic carbohydrate metabolism in male Fischer-344 rats. The data indicate that PFDA-treated rats display an inhibition in hepatic [1-13C]glucose and [3-13C]alanine utilization on day 5 posttrea...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00037a003

    authors: Goecke CM,Jarnot BM,Reo NV

    更新日期:1994-01-01 00:00:00

  • Immunochemical Detection of Protein Modification Derived from Metabolic Activation of 8-Epidiosbulbin E Acetate.

    abstract::Furanoid 8-epidiosbulbin E acetate (EEA) is one of the most abundant diterpenoid lactones in herbal medicine Dioscorea bulbifera L. (DB). Our early work proved that EEA could be metabolized to EEA-derived cis-enedial (EDE), a reactive intermediate, which is required for the hepatotoxicity observed in experimental anim...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.0c00016

    authors: Zhou S,Zhang N,Hu Z,Lin D,Li W,Peng Y,Zheng J

    更新日期:2020-07-20 00:00:00

  • Further insights into the influence of L-cysteine on the oxidation chemistry of dopamine: reaction pathways of potential relevance to Parkinson's disease.

    abstract::The initial step in the genesis of neuromelanin, a black polymeric pigment normally found in the cytoplasm of dopaminergic cell bodies in the substantia nigra (SN), is the autoxidation of dopamine (DA) to DA-o-quinone (1). In this investigation, it is demonstrated that in the presence of L-cysteine (CySH) o-quinone 1 ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx960008f

    authors: Shen XM,Dryhurst G

    更新日期:1996-06-01 00:00:00

  • Disulfiram is a potent inhibitor of proteases of the caspase family.

    abstract::We have recently shown that dithiocarbamate (DC) disulfides inhibit proteolytic processing of the caspase-3 proenzyme in Jurkat T lymphocytes treated with anti-CD95 (Fas/APO-1) antibody. Because the processing can be accomplished by caspase activity, we investigated the effect of DC disulfides, such as disulfiram (DSF...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx970131m

    authors: Nobel CS,Kimland M,Nicholson DW,Orrenius S,Slater AF

    更新日期:1997-12-01 00:00:00

  • Coumarin metabolism by rat esophageal microsomes and cytochrome P450 2A3.

    abstract::The rat esophagus is strikingly sensitive to tumor induction by nitrosamines, and it has been hypothesized that this tissue contains cytochrome P450 enzymes (P450s) which catalyze the metabolic activation of these carcinogens. The metabolic capacity of the esophagus is not well characterized. In the study described he...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx010065v

    authors: von Weymarn LB,Murphy SE

    更新日期:2001-10-01 00:00:00

  • Neuroprotection in the MPTP Parkinsonian C57BL/6 mouse model by a compound isolated from tobacco.

    abstract::Epidemiological evidence suggests a lower incidence of Parkinson's disease in smokers than in nonsmokers. This evidence, together with the lower levels of brain monoamine oxidase (MAO) activity in smokers and the potential neuroprotective properties of MAO inhibitors, prompted studies which led to the isolation and ch...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx000224v

    authors: Castagnoli KP,Steyn SJ,Petzer JP,Van der Schyf CJ,Castagnoli N Jr

    更新日期:2001-05-01 00:00:00

  • Particulate depleted uranium is cytotoxic and clastogenic to human lung cells.

    abstract::Depleted uranium (DU) is commonly used in military armor and munitions, and thus, exposure of soldiers and non-combatants is potentially frequent and widespread. DU is considered a suspected human carcinogen, affecting the bronchial cells of the lung. However, few investigations have studied DU in human bronchial cell...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx700026r

    authors: Wise SS,Thompson WD,Aboueissa AM,Mason MD,Wise JP Sr

    更新日期:2007-05-01 00:00:00

  • Synthesis of nucleosides and oligonucleotides containing adducts of acrolein and vinyl chloride.

    abstract::Vinyl chloride and acrolein are important industrial chemicals. Both form DNA adducts, vinyl chloride after enzymatic oxidation to chlorooxirane and acrolein by direct reaction. Reaction at the N(2) position of guanine is a major pathway. The resulting 2-oxoethyl and 3-oxopropyl adducts cyclize spontaneously to hydrox...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx990167+

    authors: Nechev LV,Harris CM,Harris TM

    更新日期:2000-05-01 00:00:00

  • Role of P450 1A1 and P450 1A2 in bioactivation versus detoxication of the renal carcinogen aristolochic acid I: studies in Cyp1a1-/-, Cyp1a2-/-, and Cyp1a1/1a2-/- mice.

    abstract::Exposure to aristolochic acid I (AAI) is associated with aristolochic acid nephropathy, Balkan endemic nephropathy, and urothelial cancer. Individual differences in xenobiotic-metabolizing enzyme activities are likely to be a reason for interindividual susceptibility to AA-induced disease. We evaluated the reductive a...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx200259y

    authors: Arlt VM,Levová K,Bárta F,Shi Z,Evans JD,Frei E,Schmeiser HH,Nebert DW,Phillips DH,Stiborová M

    更新日期:2011-10-17 00:00:00

  • Stereostructure and biological activity of 42-hydroxy-palytoxin: a new palytoxin analogue from Hawaiian Palythoa subspecies.

    abstract::This paper reports on the analysis of the toxin content from Palythoa tuberculosa and Palythoa toxica samples collected off of the Hawaiian coast. Our work, based on in-depth high-resolution liquid chromatography-mass spectrometry analysis along with extensive NMR study, led us to structurally characterize 42-hydroxy-...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx900259v

    authors: Ciminiello P,Dell'aversano C,Dello Iacovo E,Fattorusso E,Forino M,Grauso L,Tartaglione L,Florio C,Lorenzon P,De Bortoli M,Tubaro A,Poli M,Bignami G

    更新日期:2009-11-01 00:00:00

  • Analysis of 3'-phosphoglycolaldehyde residues in oxidized DNA by gas chromatography/negative chemical ionization/mass spectrometry.

    abstract::Deoxyribose oxidation in DNA represents a biologically important facet of oxidative DNA damage that gives rise to protein-DNA cross-links and base adducts. Toward the goal of quantifying deoxyribose oxidation chemistry in cells, we report a method for the quantification of 3'-phosphoglycolaldehyde (PGA) residues, whic...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx0341198

    authors: Collins C,Awada MM,Zhou X,Dedon PC

    更新日期:2003-12-01 00:00:00

  • Profiling the reactive metabolites of xenobiotics using metabolomic technologies.

    abstract::A predominant pathway of xenobiotic-induced toxicity is initiated by bioactivation. Characterizing reactive intermediates will provide information on the structure of reactive species, thereby defining a potential bioactivation mechanism. Because most reactive metabolites are not stable, it is difficult to detect them...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx200033v

    authors: Li F,Lu J,Ma X

    更新日期:2011-05-16 00:00:00

  • Oxidative activation of thiacetazone by the Mycobacterium tuberculosis flavin monooxygenase EtaA and human FMO1 and FMO3.

    abstract::Thiacetazone (TAZ) and ethionamide (ETA) are, respectively, thiourea- and thioamide-containing second line antitubercular prodrugs for which there is an extensive clinical history of cross-resistance in Mycobacterium tuberculosis. EtaA, a recently identified flavin-containing monooxygenase (FMO), is responsible for th...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx050328b

    authors: Qian L,Ortiz de Montellano PR

    更新日期:2006-03-01 00:00:00

  • Detoxication pathways involving glutathione and epoxide hydrolase in the in vitro metabolism of chloroprene.

    abstract::Chloroprene (2-chloro-1,3-butadiene, 1) is an important industrial chemical, which is carcinogenic in experimental animals and possibly in humans. It is metabolized to the monoepoxides, 2-chloro-2-ethenyloxirane (2a,b) and (1-chloroethenyl)oxirane (3a,b), together with electrophilic chlorinated aldehydes and ketones. ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx034107m

    authors: Munter T,Cottrell L,Golding BT,Watson WP

    更新日期:2003-10-01 00:00:00

  • Liquid chromatography electrospray-mass spectrometry of urinary aflatoxin biomarkers: characterization and application to dosimetry and chemoprevention in rats.

    abstract::A liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS) method for the measurement of aflatoxin biomarkers in urine has been developed and validated. The two major aflatoxin-DNA adducts formed in rat tissues, aflatoxin N(7)-guanine and its imidazole ring opened derivative, 8,9-dihydro-8-(2,6-diami...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx010063a

    authors: Walton M,Egner P,Scholl PF,Walker J,Kensler TW,Groopman JD

    更新日期:2001-07-01 00:00:00

  • Nitric oxide produced endogenously is responsible for hypoxia-induced HIF-1α stabilization in colon carcinoma cells.

    abstract::Hypoxia-inducible factor-1α (HIF-1α) is a critical regulator of cellular responses to hypoxia. Under normoxic conditions, the cellular HIF-1α level is regulated by hydroxylation by prolyl hydroxylases (PHDs), ubiquitylation, and proteasomal degradation. During hypoxia, degradation decreases, and its intracellular leve...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx300274a

    authors: Chowdhury R,Godoy LC,Thiantanawat A,Trudel LJ,Deen WM,Wogan GN

    更新日期:2012-10-15 00:00:00

  • Antibody recognition of melphalan adducts characterized using immobilized DNA: enhanced alkylation of G-Rich regions in cells compared to in vitro.

    abstract::The bifunctional alkylating agent, melphalan, forms adducts on DNA that are recognized by two previously described monoclonal antibodies, MP5/73 and Amp4/42. Immunoreactivity to MP5/73 was lost when alkylated DNA was exposed to alkaline pH, while Amp4/42 only recognized the structures formed after the alkali treatment...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx000178z

    authors: McCartney H,Martin AM,Middleton PG,Tilby MJ

    更新日期:2001-01-01 00:00:00

  • Investigations on the effect of O(6)-benzylguanine on the formation of dG-dC interstrand cross-links induced by chloroethylnitrosoureas in human glioma cells using stable isotope dilution high-performance liquid chromatography electrospray ionization tand

    abstract::Chloroethylnitrosoureas (CENUs) are bifunctional alkylating agents widely used for the clinical treatment of cancer. They exert anticancer activity by inducing DNA interstrand cross-links (ICLs) within GC base pairs to form dG-dC cross-links. This lesion inhibits DNA double strand separation during replication and tra...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx500143b

    authors: Sun G,Zhao L,Fan T,Li S,Zhong R

    更新日期:2014-07-21 00:00:00

  • Nanomaterials and Innate Immunity: A Perspective of the Current Status in Nanosafety.

    abstract::Human exposure to engineered nanomaterials (ENMs) is inevitable due to the plethora of applications for which they are being manufactured and integrated within. ENMs demonstrate plentiful advantages in terms of industrial approaches as well as from a consumer perspective. However, despite such positives, doubts remain...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.0c00051

    authors: Cronin JG,Jones N,Thornton CA,Jenkins GJS,Doak SH,Clift MJD

    更新日期:2020-05-18 00:00:00

  • Determination of in vitro- and in vivo-formed DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline by capillary liquid chromatography/microelectrospray mass spectrometry.

    abstract::Capillary liquid chromatography/microelectrospray mass spectrometry has been applied to the detection of deoxyribonucleoside adducts of the food-derived mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) from in vitro and in vivo sources. Constant neutral loss (CNL) and selective reaction monitoring (SRM) techniques...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx990060m

    authors: Gangl ET,Turesky RJ,Vouros P

    更新日期:1999-10-01 00:00:00

  • A molecular motif required for the activation of rat neutrophil phospholipase A(2) by organochlorine compounds.

    abstract::Organochlorine (OC) compounds are some of the main toxicants present in the food web and target several cellular systems including the nonspecific immune system. The objective of this study was to test the hypothesis that OC compounds that activate neutrophils share common structural features. Using activation of phos...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx0155449

    authors: Olivero J,Bezdecny SA,Ganey PE

    更新日期:2002-02-01 00:00:00

  • Lipid peroxidation-dependent chemiluminescence from the cyclization of alkylperoxyl radicals to dioxetane radical intermediates.

    abstract::This work reveals a novel mechanism for triplet carbonyl formation (and hence chemiluminescence) during lipid peroxidation, whose chemiluminescence has been attributed to both triplet carbonyls and singlet oxygen. As a model for polyunsaturated fatty acid hydroperoxides, we have synthesized 3-hydroperoxy-2,3-dimethyl-...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx970075p

    authors: Tímmins GS,dos Santos RE,Whitwood AC,Catalani LH,Di Mascio P,Gilbert BC,Bechara EJ

    更新日期:1997-10-01 00:00:00

  • Common E-Cigarette Flavoring Chemicals Impair Neutrophil Phagocytosis and Oxidative Burst.

    abstract::E-cigarette flavorings have not been thoroughly evaluated for inhalational toxicity. We have shown that the flavoring chemical cinnamaldehyde impairs human neutrophils, macrophages, and natural killer cells. Here we investigated the effects of other common e-liquid flavoring chemicals on phagocytosis and oxidative bur...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.9b00171

    authors: Hickman E,Herrera CA,Jaspers I

    更新日期:2019-06-17 00:00:00

  • Metabolic studies on the nigrostriatal toxin MPTP and its MAO B generated dihydropyridinium metabolite MPDP+.

    abstract::The metabolic fates of the nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its two-electron oxidation product, the 1-methyl-4-phenyl-2,3-dihydropyridinium species (MPDP+), have been examined in mouse brain and liver tissue fractions. Incubations of MPTP (50 microM and 1 mM) with mouse brain...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00003a010

    authors: Wu E,Shinka T,Caldera-Munoz P,Yoshizumi H,Trevor A,Castagnoli N Jr

    更新日期:1988-05-01 00:00:00

  • Covalent Modification of CDK2 by 4-Hydroxynonenal as a Mechanism of Inhibition of Cell Cycle Progression.

    abstract::Oxidative stress is a contributing factor in a number of chronic diseases, including cancer, atherosclerosis, and neurodegenerative diseases. Lipid peroxidation that occurs during periods of oxidative stress results in the formation of lipid electrophiles, which can modify a multitude of proteins in the cell. 4-Hydrox...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.5b00485

    authors: Camarillo JM,Rose KL,Galligan JJ,Xu S,Marnett LJ

    更新日期:2016-03-21 00:00:00

  • Proteins modified by the lipid peroxidation aldehyde 9,12-dioxo-10(E)-dodecenoic acid in MCF7 breast cancer cells.

    abstract::The hydroperoxide of linoleic acid (13-HPODE) degrades to 9,12-dioxo-10(E)-dodecenoic acid (DODE), which readily modifies proteins. This study identified the major proteins in MCF7 cells modified by DODE. To reduce false positives, three methods were used to identify DODE-modified proteins. First, cells were treated w...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx9002808

    authors: Slade PG,Williams MV,Brahmbhatt V,Dash A,Wishnok JS,Tannenbaum SR

    更新日期:2010-03-15 00:00:00