Selective cleavage of kinetoplast DNA minicircles promoted by antitrypanosomal drugs.

Abstract:

:Pentamidine, diminazene aceturate (Berenil), isometamidium chloride (Samorin), and ethidium bromide, which are important antitrypanosomal drugs, promote linearization of Trypanosoma equiperdum minicircle DNA (the principal component of kinetoplast DNA, the mitochondrial DNA in these parasites). This effect occurs at therapeutically relevant concentrations. The linearized minicircles are protease sensitive and are not digested by lambda exonuclease (a 5' to 3' exonuclease), indicating that the break is double stranded and that protein is bound to both 5' ends of the molecule. The cleavage sites map to discrete positions in the minicircle sequence, and the cleavage pattern varies with different drugs. These findings are characteristic for type II topoisomerase inhibitors, and they mimic the effects of the antitumor drug etoposide (VP16-213, a semisynthetic podophyllotoxin analog) on T. equiperdum minicircles. However, the antitrypanosomal drugs differ dramatically from etoposide in that they do not promote detectable formation of nuclear DNA-protein complexes or of strand breaks in nuclear DNA. Selective inhibition of a mitochondrial type II topoisomerase may explain why these antitrypanosomal drugs preferentially disrupt mitochondrial DNA structure and generate dyskinetoplastic trypanosomes (which lack mitochondrial DNA).

authors

Shapiro TA,Englund PT

doi

10.1073/pnas.87.3.950

subject

Has Abstract

pub_date

1990-02-01 00:00:00

pages

950-4

issue

3

eissn

0027-8424

issn

1091-6490

journal_volume

87

pub_type

杂志文章
  • Estrogens protect pancreatic beta-cells from apoptosis and prevent insulin-deficient diabetes mellitus in mice.

    abstract::In diabetes, the death of insulin-producing beta-cells by apoptosis leads to insulin deficiency. The lower prevalence of diabetes in females suggests that female sex steroids protect from beta-cell injury. Consistent with this hypothesis, 17beta-estradiol (estradiol) manifests antidiabetic actions in humans and rodent...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0602956103

    authors: Le May C,Chu K,Hu M,Ortega CS,Simpson ER,Korach KS,Tsai MJ,Mauvais-Jarvis F

    更新日期:2006-06-13 00:00:00

  • Alterations of the outer membrane composition in Escherichia coli lacking the histone-like protein HU.

    abstract::Escherichia coli cells lacking the histone-like protein HU form filaments and have an abnormal number of anucleate cells. Furthermore, their phenotype resembles that of rfa mutants, the well-characterized deep-rough phenotype, as they show an enhanced permeability that renders them hypersensitive to chloramphenicol, n...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.13.6712

    authors: Painbeni E,Caroff M,Rouviere-Yaniv J

    更新日期:1997-06-24 00:00:00

  • Myocardial pressure overload induces systemic inflammation through endothelial cell IL-33.

    abstract::Hypertension increases the pressure load on the heart and is associated with a poorly understood chronic systemic inflammatory state. Interleukin 33 (IL-33) binds to membrane-bound ST2 (ST2L) and has antihypertrophic and antifibrotic effects in the myocardium. In contrast, soluble ST2 appears to act as a decoy recepto...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1424236112

    authors: Chen WY,Hong J,Gannon J,Kakkar R,Lee RT

    更新日期:2015-06-09 00:00:00

  • The diploid genome sequence of Candida albicans.

    abstract::We present the diploid genome sequence of the fungal pathogen Candida albicans. Because C. albicans has no known haploid or homozygous form, sequencing was performed as a whole-genome shotgun of the heterozygous diploid genome in strain SC5314, a clinical isolate that is the parent of strains widely used for molecular...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0401648101

    authors: Jones T,Federspiel NA,Chibana H,Dungan J,Kalman S,Magee BB,Newport G,Thorstenson YR,Agabian N,Magee PT,Davis RW,Scherer S

    更新日期:2004-05-11 00:00:00

  • HLA-linked congenital adrenal hyperplasia results from a defective gene encoding a cytochrome P-450 specific for steroid 21-hydroxylation.

    abstract::We have determined the molecular genetic basis of congenital adrenal hyperplasia due to 21-hydroxylase (21-OHase) deficiency. This common disorder of cortisol biosynthesis is HLA-linked. The haplotype HLA-(A3);Bw47;DR7 is strongly associated with 21-OHase deficiency and always carries a null allele at the locus encodi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.23.7505

    authors: White PC,New MI,Dupont B

    更新日期:1984-12-01 00:00:00

  • Insulin receptors in human circulating cells and fibroblasts.

    abstract::Human lymphocytes obtained from fasted adult subjects and cultured human tumor lymphocytes were investigated for specific insulin receptors. By use of monoiodoinsulin, specific insulin binding sites were demonstrated in peripheral human lymphocytes, cultured human lymphocytes, and in other types of human circulating c...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.69.3.747

    authors: Gavin JR 3rd,Roth J,Jen P,Freychet P

    更新日期:1972-03-01 00:00:00

  • Pay-what-you-want, identity, and self-signaling in markets.

    abstract::We investigate the role of identity and self-image consideration under "pay-what-you-want" pricing. Results from three field experiments show that often, when granted the opportunity to name the price of a product, fewer consumers choose to buy it than when the price is fixed and low. We show that this opt-out behavio...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1120893109

    authors: Gneezy A,Gneezy U,Riener G,Nelson LD

    更新日期:2012-05-08 00:00:00

  • Site-specific ubiquitination is required for relieving the transcription factor Miz1-mediated suppression on TNF-α-induced JNK activation and inflammation.

    abstract::The transcription factor zinc-finger protein Miz1 represses TNF-α-induced JNK activation and the repression is relieved upon TNF-α stimulation. However, the underlying mechanism is incompletely understood. Here we report that Miz1 interferes with the ubiquitin conjugating enzyme (E2) Ubc13 for binding to the RING doma...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1105176108

    authors: Liu J,Yan J,Jiang S,Wen J,Chen L,Zhao Y,Lin A

    更新日期:2012-01-03 00:00:00

  • Structure and assembly of an augmented Sm-like archaeal protein 14-mer.

    abstract::To better understand the roles of Sm proteins in forming the cores of many RNA-processing ribonucleoproteins, we determined the crystal structure of an atypical Sm-like archaeal protein (SmAP3) in which the conserved Sm domain is augmented by a previously uncharacterized, mixed alpha/beta C-terminal domain. The struct...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0538042100

    authors: Mura C,Phillips M,Kozhukhovsky A,Eisenberg D

    更新日期:2003-04-15 00:00:00

  • Large electrical currents traverse developing Ceropia follicles.

    abstract::An intense (up to 20 muA/cm(2)) steady electrical current enters the anterior or nurse cell end of the growing follicle (or oocyte-nurse cell complex) of the Cecropia moth and is balanced by a more diffuse current leaving elsewhere. In late growth stages, the total transfollicular current is about 100 nA. Moreover, a ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.3.1328

    authors: Jaffe LF,Woodruff RI

    更新日期:1979-03-01 00:00:00

  • Achievements and challenges in the biology of environmental effects.

    abstract::The starting point for the study of adverse experiences is that some have enduring consequences that continue after the period of exposure to the adversity. That raises four basic issues: whether social adversities can be considered homogeneous, whether the crucial effect lies in the "objective" or subjectively percei...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.1121258109

    authors: Rutter M

    更新日期:2012-10-16 00:00:00

  • Identification of icsA, a plasmid locus of Shigella flexneri that governs bacterial intra- and intercellular spread through interaction with F-actin.

    abstract::The capacity of Shigella to spread within the cytosol of infected epithelial cells and to infect adjacent cells is critical for the development of infection foci, which lead to mucosal abscesses. Shigella is a nonmotile microorganism that appears to utilize host cell microfilaments to generate intra- as well as interc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.10.3867

    authors: Bernardini ML,Mounier J,d'Hauteville H,Coquis-Rondon M,Sansonetti PJ

    更新日期:1989-05-01 00:00:00

  • New evidence on the impact of sustained exposure to air pollution on life expectancy from China's Huai River Policy.

    abstract::This paper finds that a 10-μg/m3 increase in airborne particulate matter [particulate matter smaller than 10 μm (PM10)] reduces life expectancy by 0.64 years (95% confidence interval = 0.21-1.07). This estimate is derived from quasiexperimental variation in PM10 generated by China's Huai River Policy, which provides f...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1616784114

    authors: Ebenstein A,Fan M,Greenstone M,He G,Zhou M

    更新日期:2017-09-26 00:00:00

  • Human apolipoprotein E expression in Escherichia coli: structural and functional identity of the bacterially produced protein with plasma apolipoprotein E.

    abstract::Human apolipoprotein E (apoE) was produced in Escherichia coli by transforming cells with an expression vector containing a reconstructed apoE cDNA, a lambda PL promoter regulated by the thermolabile cI repressor, and a ribosomal binding site derived from the lambda cII or the E. coli beta-lactamase gene. Transformed ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.24.8696

    authors: Vogel T,Weisgraber KH,Zeevi MI,Ben-Artzi H,Levanon AZ,Rall SC Jr,Innerarity TL,Hui DY,Taylor JM,Kanner D

    更新日期:1985-12-01 00:00:00

  • Heterogeneities in the transmission of infectious agents: implications for the design of control programs.

    abstract::From an analysis of the distributions of measures of transmission rates among hosts, we identify an empirical relationship suggesting that, typically, 20% of the host population contributes at least 80% of the net transmission potential, as measured by the basic reproduction number, R0. This is an example of a statist...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.1.338

    authors: Woolhouse ME,Dye C,Etard JF,Smith T,Charlwood JD,Garnett GP,Hagan P,Hii JL,Ndhlovu PD,Quinnell RJ,Watts CH,Chandiwana SK,Anderson RM

    更新日期:1997-01-07 00:00:00

  • Crystal structures that suggest late development of genetic code components for differentiating aromatic side chains.

    abstract::Early forms of the genetic code likely generated "statistical" proteins, with similar side chains occupying the same sequence positions at different ratios. In this scenario, groups of related side chains were treated by aminoacyl-tRNA synthetases as a single molecular species until a discrimination mechanism develope...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2136794100

    authors: Yang XL,Otero FJ,Skene RJ,McRee DE,Schimmel P,Ribas de Pouplana L

    更新日期:2003-12-23 00:00:00

  • Two types of magnetic shape-memory effects from twinned microstructure and magneto-structural coupling in Fe1+y Te.

    abstract::A detailed experimental investigation of Fe1+y Te (y = 0.11, 0.12) using pulsed magnetic fields up to 60 T confirms remarkable magnetic shape-memory (MSM) effects. These effects result from magnetoelastic transformation processes in the low-temperature antiferromagnetic state of these materials. The observation of mod...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1905271116

    authors: Rößler S,Koz C,Wang Z,Skourski Y,Doerr M,Kasinathan D,Rosner H,Schmidt M,Schwarz U,Rößler UK,Wirth S

    更新日期:2019-08-20 00:00:00

  • 7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide: a partial modulator of AMPA receptor desensitization devoid of neurotoxicity.

    abstract::In cerebellar granule neurons of neonatal rats micromolar concentrations of 7-chloro-3-methyl-3,4-dihydro-2H-1,2, 4-benzothiadiazine S,S-dioxide (IDRA-21) and cyclothiazide, two negative modulators of the spontaneous agonist-dependent rapid desensitization of alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.13.7053

    authors: Impagnatiello F,Oberto A,Longone P,Costa E,Guidotti A

    更新日期:1997-06-24 00:00:00

  • Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells.

    abstract::The vascular endothelial growth factor (VEGF) family has recently expanded by the identification and cloning of three additional members, namely VEGF-B, VEGF-C, and VEGF-D. In this study we demonstrate that VEGF-B binds selectively to VEGF receptor-1/Flt-1. This binding can be blocked by excess VEGF, indicating that t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.20.11709

    authors: Olofsson B,Korpelainen E,Pepper MS,Mandriota SJ,Aase K,Kumar V,Gunji Y,Jeltsch MM,Shibuya M,Alitalo K,Eriksson U

    更新日期:1998-09-29 00:00:00

  • Dissection of the insulin signaling pathway via quantitative phosphoproteomics.

    abstract::The insulin signaling pathway is of pivotal importance in metabolic diseases, such as diabetes, and in cellular processes, such as aging. Insulin activates a tyrosine phosphorylation cascade that branches to create a complex network affecting multiple biological processes. To understand the full spectrum of the tyrosi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0711713105

    authors: Krüger M,Kratchmarova I,Blagoev B,Tseng YH,Kahn CR,Mann M

    更新日期:2008-02-19 00:00:00

  • ABL kinase inhibition promotes lung regeneration through expansion of an SCGB1A1+ SPC+ cell population following bacterial pneumonia.

    abstract::Current therapeutic interventions for the treatment of respiratory infections are hampered by the evolution of multidrug resistance in pathogens as well as the lack of effective cellular targets. Despite the identification of multiple region-specific lung progenitor cells, the identity of molecules that might be thera...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1816030116

    authors: Khatri A,Kraft BD,Tata PR,Randell SH,Piantadosi CA,Pendergast AM

    更新日期:2019-01-29 00:00:00

  • Photoaffinity labeling of indole-3-acetic acid-binding proteins in maize.

    abstract::The photoaffinity labeling agent 5-azidoindole-3-acetic acid, an analog of the endogenous plant hormone indole-3-acetic acid (an auxin), was used to identify indole-3-acetic acid-binding proteins in maize. Two peptides with subunit molecular masses of 24 and 22 kilodaltons are specifically labeled in a saturable manne...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.16.6153

    authors: Jones AM,Venis MA

    更新日期:1989-08-01 00:00:00

  • Ultrasensitive fluorometric detection of carbohydrates as derivatives in mixtures separated by capillary electrophoresis.

    abstract::Reducing monosaccharides and oligosaccharides, after reductive amination, were separated and detected as their 3-(4-carboxybenzoyl)-2-quinolinecarboxaldehyde (CBQCA) derivatives by capillary electrophoresis/laser-induced fluorescence. Under optimized conditions, the minimum detectable quantities for monosaccharide sol...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.6.2302

    authors: Liu JP,Shirota O,Wiesler D,Novotny M

    更新日期:1991-03-15 00:00:00

  • Interaction of the Wiskott-Aldrich syndrome protein with sorting nexin 9 is required for CD28 endocytosis and cosignaling in T cells.

    abstract::The Wiskott-Aldrich syndrome protein (WASp) plays a major role in coupling T cell antigen receptor (TCR) stimulation to induction of actin cytoskeletal changes required for T cell activation. Here, we report that WASp inducibly binds the sorting nexin 9 (SNX9) in T cells and that WASp, SNX9, p85, and CD28 colocalize w...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0610543104

    authors: Badour K,McGavin MK,Zhang J,Freeman S,Vieira C,Filipp D,Julius M,Mills GB,Siminovitch KA

    更新日期:2007-01-30 00:00:00

  • Coordinated motor output in the hindlimb of the 7-day chick embryo.

    abstract::Electromyographic recordings from individual identified ankle muscles of the 7-day chick embryo (stage 31) were used to determine the organization of motor output at a developmental stage shortly after the onset of spontaneous motility in the leg. During spontaneous motility of the embryo, the electromyographic record...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.4.1245

    authors: Bekoff A,Stein PS,Hamburger V

    更新日期:1975-04-01 00:00:00

  • Application of the chloro ketal Claisen reaction to the total synthesis of squalene.

    abstract::A short, highly stereoselective (over 97%) synthesis of all-trans squalene is described. Starting with succinaldehyde, a tetraenedichlorodione having the complete squalene skeleton with the four internal trans olefinic bonds has been developed in four steps involving a sequence of two double Claisen rearrangements. Th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.67.3.1465

    authors: Werthemann L,Johnson WS

    更新日期:1970-11-01 00:00:00

  • The gametic central cell of Arabidopsis determines the lifespan of adjacent accessory cells.

    abstract::Plant germ cells develop in specialized haploid structures, termed gametophytes. The female gametophyte patterns of flowering plants are diverse, with often unknown adaptive value. Here we present the Arabidopsis fiona mutant, which forms a female gametophyte that is structurally and functionally reminiscent of a phyl...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1012795108

    authors: Kägi C,Baumann N,Nielsen N,Stierhof YD,Gross-Hardt R

    更新日期:2010-12-21 00:00:00

  • Atomic structure of a rhinovirus C, a virus species linked to severe childhood asthma.

    abstract::Isolates of rhinovirus C (RV-C), a recently identified Enterovirus (EV) species, are the causative agents of severe respiratory infections among children and are linked to childhood asthma exacerbations. The RV-C have been refractory to structure determination because they are difficult to propagate in vitro. Here, we...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1606595113

    authors: Liu Y,Hill MG,Klose T,Chen Z,Watters K,Bochkov YA,Jiang W,Palmenberg AC,Rossmann MG

    更新日期:2016-08-09 00:00:00

  • Translocation of a folded protein across the outer membrane in Escherichia coli.

    abstract::A mutation in the Escherichia coli dsbA gene (coding for a periplasmic disulfide oxidoreductase) reduces the rate of disulfide bond formation in the enzyme pullulanase and also reduces the rate at which the enzyme is secreted to the cell surface, as measured by protease accessibility. The enzyme did not become proteas...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.24.12058

    authors: Pugsley AP

    更新日期:1992-12-15 00:00:00

  • Pervasive Arctic lead pollution suggests substantial growth in medieval silver production modulated by plague, climate, and conflict.

    abstract::Lead pollution in Arctic ice reflects large-scale historical changes in midlatitude industrial activities such as ancient lead/silver production and recent fossil fuel burning. Here we used measurements in a broad array of 13 accurately dated ice cores from Greenland and Severnaya Zemlya to document spatial and tempor...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1904515116

    authors: McConnell JR,Chellman NJ,Wilson AI,Stohl A,Arienzo MM,Eckhardt S,Fritzsche D,Kipfstuhl S,Opel T,Place PF,Steffensen JP

    更新日期:2019-07-23 00:00:00