In vivo effects of mercury (II) on deoxyuridine triphosphate nucleotidohydrolase, DNA polymerase (alpha, beta), and uracil-DNA glycosylase activities in cultured human cells: relationship to DNA damage, DNA repair, and cytotoxicity.

Abstract:

:The effect of mercuric acetate on the activities of deoxyuridine triphosphate nucleotidohydrolase (dUTPase), DNA polymerase (alpha, beta), and uracil-DNA glycosylase has been studied in cultured human KB cells. There was a dose- and time-dependent inactivation of both dUTPase and DNA polymerase alpha activities by mercuric acetate. In cells exposed to low concentrations (10 microM) of mercuric acetate, dUTPase was most sensitive to inhibition with 30% of the activity being inhibited after a 1-hr exposure. At higher concentrations or for longer exposure times, DNA polymerase alpha was most sensitive to inhibition with greater than 60% of the activity being inhibited by 25 microM mercuric acetate after a 15-min exposure. There was no inhibition of DNA polymerase beta or uracil-DNA glycosylase activities in cells exposed to 50 microM mercuric acetate for 90 min. In fact, there was a time- and dose-dependent activation of uracil-DNA glycosylase activity with maximum activation occurring in cells exposed to 50 microM mercuric acetate. The inhibition of dUTPase and DNA polymerase alpha activities and the activation of uracil-DNA glycosylase activity correlated with the induction of single-strand breaks in DNA by mercuric acetate and with the decrease in cell viability.

journal_name

Mol Pharmacol

journal_title

Molecular pharmacology

authors

Williams MV,Winters T,Waddell KS

subject

Has Abstract

pub_date

1987-02-01 00:00:00

pages

200-7

issue

2

eissn

0026-895X

issn

1521-0111

journal_volume

31

pub_type

杂志文章
  • Structural basis for ether-a-go-go-related gene K+ channel subtype-dependent activation by niflumic acid.

    abstract::Niflumic acid [2-((3-(trifluoromethyl)phenyl)amino)-3-pyridinecarboxylic acid, NFA] is a nonsteroidal anti-inflammatory drug that also blocks or modulates the gating of a wide spectrum of ion channels. Here we investigated the mechanism of channel activation by NFA on ether-a-go-go-related gene (ERG) K(+) channel subt...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.107.043505

    authors: Fernandez D,Sargent J,Sachse FB,Sanguinetti MC

    更新日期:2008-04-01 00:00:00

  • Mutations within the cholecystokinin-B/gastrin receptor ligand 'pocket' interconvert the functions of nonpeptide agonists and antagonists.

    abstract::We have reported previously that the transmembrane domains of the cholecystokinin-B/gastrin receptor (CCK-BR) comprise a putative ligand binding pocket. In the present study, we examined whether amino acid substitutions within the CCK-BR pocket altered the affinities and/or functional activities of L-365,260 (the prot...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.54.5.857

    authors: Bläker M,Ren Y,Gordon MC,Hsu JE,Beinborn M,Kopin AS

    更新日期:1998-11-01 00:00:00

  • Myristyl trimethyl ammonium bromide and octadecyl trimethyl ammonium bromide are surface-active small molecule dynamin inhibitors that block endocytosis mediated by dynamin I or dynamin II.

    abstract::Dynamin is a GTPase enzyme involved in membrane constriction and fission during endocytosis. Phospholipid binding via its pleckstrin homology domain maximally stimulates dynamin activity. We developed a series of surface-active small-molecule inhibitors, such as myristyl trimethyl ammonium bromide (MiTMAB) and octadec...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.107.034207

    authors: Quan A,McGeachie AB,Keating DJ,van Dam EM,Rusak J,Chau N,Malladi CS,Chen C,McCluskey A,Cousin MA,Robinson PJ

    更新日期:2007-12-01 00:00:00

  • Structural requirements of analogues of polyamines for migration and growth of IEC-6 cells.

    abstract::Healing of gastrointestinal mucosal lesions occurs through two processes: an early one involving cell migration and a later one in which cell division replaces lost cells. Both processes require the presence of polyamines, but the mechanism of action of these compounds is unknown. In the present study, we examined the...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: McCormack SA,Zimmerman BJ,Israel M,Blanner P,Johnson LR

    更新日期:1995-10-01 00:00:00

  • A single conservative amino acid substitution in the reverse transcriptase of human immunodeficiency virus-1 confers resistance to (+)-(5S)-4,5,6,7-tetrahydro-5-methyl-6-(3-methyl-2-butenyl)imidazo[4,5, 1- jk][1,4]benzodiazepin-2(1H)-thione (TIBO R82150).

    abstract::Tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one and -thione (TIBO) derivatives (e.g., R82150) are potent, human immunodeficiency virus-1 (HIV-1)-specific, inhibitors of reverse transcriptase (RT) that are undergoing initial evaluation in clinical trials. Because HIV-1 has become resistant to other RT inhibitor...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Mellors JW,Im GJ,Tramontano E,Winkler SR,Medina DJ,Dutschman GE,Bazmi HZ,Piras G,Gonzalez CJ,Cheng YC

    更新日期:1993-01-01 00:00:00

  • Activation of retinoic acid receptors by dihydroretinoids.

    abstract::Vitamin A-derived metabolites act as ligands for nuclear receptors controlling the expression of a number of genes. Stereospecific saturation of the C(13)-C(14) double bond of all-trans-retinol by the enzyme, retinol saturase (RetSat), leads to the production of (R)-all-trans-13,14-dihydroretinol. In liver and adipose...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.109.060038

    authors: Moise AR,Alvarez S,Domínguez M,Alvarez R,Golczak M,Lobo GP,von Lintig J,de Lera AR,Palczewski K

    更新日期:2009-12-01 00:00:00

  • Tityustoxin-K alpha, a structurally novel and highly potent K+ channel peptide toxin, interacts with the alpha-dendrotoxin binding site on the cloned Kv1.2 K+ channel.

    abstract::The interaction between two nonhomologous K+ channel toxins, Tityus serrulatus (scorpion) toxin tityustoxin-K alpha (TsTX-K alpha) and Dendroaspis angusticeps (snake) toxin dendrotoxin (alpha-DTX), was investigated on K+ currents in B82 fibroblast cells transformed to express the Kv1.2 K+ channel. As demonstrated prev...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Werkman TR,Gustafson TA,Rogowski RS,Blaustein MP,Rogawski MA

    更新日期:1993-08-01 00:00:00

  • Lipoxygenase metabolites as mediators of UTP-induced intracellular acidification in mouse RAW 264.7 macrophages.

    abstract::In previous studies, we have shown that mouse RAW 264.7 macrophages possess pyrimidinoceptors, coupled to a phosphoinositide-specific phospholipase C, with a higher specificity for UTP than for ATP. In the current study, we explored the mechanism involved in the UTP-induced intracellular acidification seen in this cel...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.53.2.313

    authors: Lin WW,Chang SH,Wu ML

    更新日期:1998-02-01 00:00:00

  • The Role of ACKR3 in Breast, Lung, and Brain Cancer.

    abstract::Recent reports regarding the significance of chemokine receptors in disease have put a spotlight on atypical chemokine receptor 3 (ACKR3). This atypical chemokine receptor is overexpressed in numerous cancer types and has been involved in the modulation of tumor cell proliferation and migration, tumor angiogenesis, or...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1124/mol.118.115279

    authors: Neves M,Fumagalli A,van den Bor J,Marin P,Smit MJ,Mayor F

    更新日期:2019-12-01 00:00:00

  • Prolonged ethanol inhalation decreases gamma-aminobutyric acidA receptor alpha subunit mRNAs in the rat cerebral cortex.

    abstract::Ethanol administration to rats by ethanol vapor inhalation (14 days) results in a 40-50% reduction in the level of gamma-aminobutyric acidA (GABAA) receptor alpha 1 subunit mRNAs [4.4 and 4.8 kilobases (kb)] in the cerebral cortex. The level of alpha 2 subunit mRNA (8.0 kb) was also reduced by 29%, whereas there was n...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Montpied P,Morrow AL,Karanian JW,Ginns EI,Martin BM,Paul SM

    更新日期:1991-02-01 00:00:00

  • Megakaryocytic Smad4 Regulates Platelet Function through Syk and ROCK2 Expression.

    abstract::Smad4, a key transcription factor in the transforming growth factor-β signaling pathway, is involved in a variety of cell physiologic and pathologic processes. Here, we characterized megakaryocyte/platelet-specific Smad4 deficiency in mice to elucidate its effect on platelet function. We found that megakaryocyte/plate...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.116.107417

    authors: Wang Y,Jiang L,Mo X,Lan Y,Yang X,Liu X,Zhang J,Zhu L,Liu J,Wu X

    更新日期:2017-09-01 00:00:00

  • Apurinic/apyrimidinic endonuclease-1 protein level is associated with the cytotoxicity of L-configuration deoxycytidine analogs (troxacitabine and beta-L-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine) but not D-configuration deoxycytidine analogs (gemcit

    abstract::Beta-L-dioxolane-cytidine (L-OddC, BCH-4556, Troxacitabine), a novel L-configuration deoxycytidine analog, is under phase III clinical trial for cancer treatment. We showed that human apurinic/apyrimidinic endonuclease (APE-1) has exonuclease activity for preferentially removing L-OddC and other L-configuration nucleo...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.105.021527

    authors: Lam W,Park SY,Leung CH,Cheng YC

    更新日期:2006-05-01 00:00:00

  • An Ab initio study of the relationship between nitroarene mutagenicity and electron affinity.

    abstract::Electron affinities, approximated by lowest unoccupied molecular orbital (LUMO) energies, were determined for an extensive group of nitrated polycyclic aromatic hydrocarbons by ab initio methods at the STO-3G level. Significant correlations were demonstrated between nitroarene LUMO energy and the corresponding mutagen...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Maynard AT,Pedersen LG,Posner HS,McKinney JD

    更新日期:1986-06-01 00:00:00

  • GRK2 Mediates Arginine Vasopressin-Induced Interleukin-6 Production via Nuclear Factor-κB Signaling Neonatal Rat Cardiac Fibroblast.

    abstract::Interleukin 6 (IL-6), which is elevated in patients with congestive heart failure and acts as both a chronic marker of inflammation and an acute-phase reactant, is associated with myocardial damage. Circulating levels of arginine vasopressin (AVP) are elevated during cardiac stress and could be a factor for cardiac in...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.116.107698

    authors: Xu F,Sun S,Wang X,Ni E,Zhao L,Zhu W

    更新日期:2017-09-01 00:00:00

  • Agonist-promoted Lys63-linked polyubiquitination of the human kappa-opioid receptor is involved in receptor down-regulation.

    abstract::Ubiquitination of the human kappa opioid receptor (hKOR) expressed in Chinese hamster ovary (CHO) cells was observed in the presence of the proteasomal inhibitor N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal (MG132) and enhanced by the agonists (-)(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidiny) cyclohexyl] benzeneaceta...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.107.042846

    authors: Li JG,Haines DS,Liu-Chen LY

    更新日期:2008-04-01 00:00:00

  • Expression of tandem glutathione S-transferase recombinant genes in COS cells for analysis of efficiency of protein expression and associated drug resistance.

    abstract::Expression vectors were designed and constructed to achieve optimum production of two different isozymes of rat glutathione S-transferase (GST) (EC 2.5.1.18) in COS cells, for studies of drug resistance. Promoter-enhancer elements from the simian virus 40 (SV40) early-region or the mouse alpha 2(I)-collagen gene, GST ...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Manoharan TH,Welch PJ,Gulick AM,Puchalski RB,Lathrop AL,Fahl WE

    更新日期:1991-04-01 00:00:00

  • Lysophospholipid-mediated inhibition of Na+,K(+)-adenosine triphosphatase is a possible mechanism of immunosuppressive activity of cyclosporin A.

    abstract::The relationship between the phospholipase-stimulating and immunosuppressive properties of cyclosporin A (CsA) has been investigated in vitro. At concentrations of 0.025 microM and upwards, CsA caused dose-related inhibition of both mitogen- and alloantigen-stimulated uptake of tritiated thymidine by human mononuclear...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Anderson R,Smit MJ,Van Rensburg CE

    更新日期:1993-09-01 00:00:00

  • Direct evidence for the existence and functional role of hyperreactive sulfhydryls on the ryanodine receptor-triadin complex selectively labeled by the coumarin maleimide 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin.

    abstract::The fluorogenic sulfhydryl probe 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin (CPM) (1-50 nM) is used to characterize the functional role and location of highly reactive thiol groups on the ryanodine-sensitive Ca2+ release channel complex [i.e., ryanodine receptors (RyRs)] of skeletal and cardiac junctional...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Liu G,Abramson JJ,Zable AC,Pessah IN

    更新日期:1994-02-01 00:00:00

  • Tetrahydroaminoacridine block of N-methyl-D-aspartate-activated cation channels in cultured hippocampal neurons.

    abstract::The action of tetrahydroaminoacridine (THA), a centrally active cholinesterase inhibitor that may provide symptomatic benefit in Alzheimer's disease, was studied on responses to the excitatory amino acid N-methyl-D-aspartate (NMDA) in cultured hippocampal neurons, using whole-cell voltage-clamp and single-channel reco...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Hershkowitz N,Rogawski MA

    更新日期:1991-05-01 00:00:00

  • Lactone modulation of the gamma-aminobutyric acid A receptor: evidence for a positive modulatory site.

    abstract::The gamma-aminobutyric acid-A (GABA(A)) receptor complex is allosterically modulated by a variety of substances, some of clinical importance. Barbiturates and neurosteroids augment GABA-currents and also directly gate the channel. A variety of gamma-butyrolactone analogues also modulate GABA-induced currents, with som...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.52.1.114

    authors: Williams KL,Tucker JB,White G,Weiss DS,Ferrendelli JA,Covey DF,Krause JE,Rothman SM

    更新日期:1997-07-01 00:00:00

  • Sirtuin 1 Mediates the Actions of Peroxisome Proliferator-Activated Receptor δ on the Oxidized Low-Density Lipoprotein-Triggered Migration and Proliferation of Vascular Smooth Muscle Cells.

    abstract::Peroxisome proliferator-activated receptor δ (PPARδ) has been implicated in vascular pathophysiology. However, its functions in atherogenic changes of the vascular wall have not been fully elucidated. PPARδ activated by GW501516 (2-[2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]ph...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.116.104679

    authors: Hwang JS,Ham SA,Yoo T,Lee WJ,Paek KS,Lee CH,Seo HG

    更新日期:2016-11-01 00:00:00

  • Characterization of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one as a heme-site inhibitor of nitric oxide-sensitive guanylyl cyclase.

    abstract::Nitric oxide (NO) binds with high affinity to the heme of soluble guanylyl cyclase (sGC), resulting in accumulation of the second messenger cGMP in many biological systems. 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) was recently described as potent and selective inhibitor of sGC, providing an invaluable tool wi...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Schrammel A,Behrends S,Schmidt K,Koesling D,Mayer B

    更新日期:1996-07-01 00:00:00

  • N-Terminal Targeting of Regulator of G Protein Signaling Protein 2 for F-Box Only Protein 44-Mediated Proteasomal Degradation.

    abstract::Regulator of G protein signaling (RGS) proteins are negative modulators of G protein signaling that have emerged as promising drug targets to improve specificity and reduce side effects of G protein-coupled receptor-related therapies. Several small molecule RGS protein inhibitors have been identified; however, enhanci...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/molpharm.120.000061

    authors: McNabb HJ,Gonzalez S,Muli CS,Sjögren B

    更新日期:2020-12-01 00:00:00

  • Differential inhibition of multiple cAMP phosphodiesterase isozymes by isoflavones and tyrphostins.

    abstract::A series of isoflavone and tyrphostin compounds were found to inhibit the degradation of cAMP by several cyclic nucleotide phosphodiesterase (PDE) isozymes. Specific hydroxyl groups on the isoflavone structure were critical for PDE isozyme-selective inhibition. Replacement of the C-7 hydroxyl group of the isoflavone w...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.57.4.738

    authors: Nichols MR,Morimoto BH

    更新日期:2000-04-01 00:00:00

  • 3H-neurokinin A labels a specific tachykinin-binding site in the rat duodenal smooth muscle.

    abstract::3H-Neurokinin A (3H-NKA) with high specific activity (75 Ci/mmol) was synthesized to study NKA (NK-2)-binding sites on membrane preparations of various tissues in the rat, including brain, spinal cord, duodenum, vas deferens, and ileum. The binding capacity of 3H-NKA (0.9 nM) was very low in membrane preparations of d...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Bergström L,Beaujouan JC,Torrens Y,Saffroy M,Glowinski J,Lavielle S,Chassaing G,Marquet A,D'Orleans-Juste P,Dion S

    更新日期:1987-12-01 00:00:00

  • Anti-HIV activity and resistance profile of the CXC chemokine receptor 4 antagonist POL3026.

    abstract::We have studied the mechanism of action of Arg(*)-Arg-Nal(2)-Cys(1x)-Tyr-Gln-Lys-(d-Pro)-Pro-Tyr-Arg-Cit-Cys(1x)-Arg-Gly-(d-Pro)(*) (POL3026), a novel specific beta-hairpin mimetic CXC chemokine receptor (CXCR)4 antagonist. POL3026 specifically blocked the binding of anti-CXCR4 monoclonal antibody 12G5 and the intrace...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.107.042911

    authors: Moncunill G,Armand-Ugón M,Clotet-Codina I,Pauls E,Ballana E,Llano A,Romagnoli B,Vrijbloed JW,Gombert FO,Clotet B,De Marco S,Esté JA

    更新日期:2008-04-01 00:00:00

  • The multifunctional deoxynucleoside kinase of insect cells is a target for the development of new insecticides.

    abstract::The antiherpetic agent (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) was found to be an efficient substrate for recombinant Drosophila melanogaster-deoxyribonucleoside kinase with a K(m) of 4.5 microM and a V(max) of 400 nmol/microg protein/h compared with 1.3 microM and 62.5 nmol/microg protein/h, respectively, for the...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.57.4.811

    authors: Balzarini J,Degrève B,Hatse S,De Clercq E,Breuer M,Johansson M,Huybrechts R,Karlsson A

    更新日期:2000-04-01 00:00:00

  • Inhibition of Brain Epidermal Growth Factor Receptor Activation: A Novel Target in Neurodegenerative Diseases and Brain Injuries.

    abstract::Several reports have been published recently demonstrating a beneficial effect of epidermal growth factor receptor (EGFR) inhibitors in improving pathologic and behavioral conditions in neurodegenerative diseases (NDDs) such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS) as well as the brain and spinal...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1124/mol.120.119909

    authors: Tavassoly O,Sato T,Tavassoly I

    更新日期:2020-07-01 00:00:00

  • Activation of the c-jun protooncogene in human myeloid leukemia cells treated with etoposide.

    abstract::The epipodophyllotoxin etoposide is an inhibitor of topoisomerase II. The effects of this agent on gene expression, particularly the transcriptional induction of genes implicated in growth control, are unknown. The present results demonstrate that etoposide induces expression of the c-jun protooncogene in HL-60 myeloi...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Rubin E,Kharbanda S,Gunji H,Kufe D

    更新日期:1991-06-01 00:00:00

  • Late endosomal/lysosomal targeting and lack of recycling of the ligand-occupied endothelin B receptor.

    abstract::A fusion protein consisting of the endothelin B (ET(B)) receptor and the enhanced green fluorescent protein (EGFP) in conjunction with Cyanin3- or fluorescein-conjugated endothelin 1 (Cy3-ET1, Fluo-ET1) was used to investigate the ligand-mediated internalization of the ET(B) receptor. The ET(B) receptor and the ET(B)/...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Oksche A,Boese G,Horstmeyer A,Furkert J,Beyermann M,Bienert M,Rosenthal W

    更新日期:2000-06-01 00:00:00