当前位置： SCI文献检索 > ACS Chemical Biology期刊下所有文献 > Heavy Metals Induce Decline of Derivatives of 5-Methycytosine in Both DNA and RNA of Stem Cells.

Heavy Metals Induce Decline of Derivatives of 5-Methycytosine in Both DNA and RNA of Stem Cells.

Abstract：

:Toxic heavy metals have been considered to be harmful environmental contaminations. The molecular mechanisms of heavy-metals-induced cytotoxicity and carcinogenicity are still not well elucidated. Previous reports showed exposures to toxic heavy metals can cause a change of DNA cytosine methylation (5-methylcytosine, 5-mC). However, it is still not clear whether heavy metals have effects on the recently identified new epigenetic marks in both DNA and RNA, i.e., 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and 5-carboxylcytosine (5-caC). Here, we established a chemical labeling strategy in combination with liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS) analysis for highly sensitive detection of eight modified cytidines in DNA and RNA. The developed method allowed simultaneous detection of all eight modified cytidines with improved detection sensitivities of 128-443-fold. Using this method, we demonstrated that the levels of 5-hmC, 5-foC, and 5-caC significantly decreased in both the DNA and RNA of mouse embryonic stem (ES) cells while exposed to arsenic (As), cadmium (Cd), chromium (Cr), and antimony (Sb). In addition, we found that treatments by heavy metals induced a decrease of the activities of 10-11 translocation (Tet) proteins. Furthermore, we revealed that a content change of metabolites occurring in the tricarboxylic acid cycle may be responsible for the decline of the derivatives of 5-mC. Our study shed light on the epigenetic effects of heavy metals, especially for the induced decline of the derivatives of 5-mC in both DNA and RNA.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Xiong J,Liu X,Cheng QY,Xiao S,Xia LX,Yuan BF,Feng YQ

doi

10.1021/acschembio.7b00170

subject

Has Abstract

pub_date

2017-06-16 00:00:00

pages

1636-1643

issue

6

eissn

1554-8929

issn

1554-8937

journal_volume

12

pub_type

杂志文章

相关文献

ACS Chemical Biology文献大全
  • Development of a selective activity-based probe for adenylating enzymes: profiling MbtA Involved in siderophore biosynthesis from Mycobacterium tuberculosis.

    abstract：:MbtA is an adenylating enzyme from Mycobacterium tuberculosis that catalyzes the first step in the biosynthesis of the mycobactins. A bisubstrate inhibitor of MbtA (Sal-AMS) was previously described that displays potent antitubercular activity under iron-replete as well as iron-deficient growth conditions. This findin...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb300112x

    authors： Duckworth BP,Wilson DJ,Nelson KM,Boshoff HI,Barry CE 3rd,Aldrich CC

    更新日期：2012-10-19 00:00:00

  • Harnessing Fluorine-Sulfur Contacts and Multipolar Interactions for the Design of p53 Mutant Y220C Rescue Drugs.

    abstract：:Many oncogenic mutants of the tumor suppressor p53 are conformationally unstable, including the frequently occurring Y220C mutant. We have previously developed several small-molecule stabilizers of this mutant. One of these molecules, PhiKan083, 1-(9-ethyl-9H-carbazole-3-yl)-N-methylmethanamine, binds to a mutation-in...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.6b00315

    authors： Bauer MR,Jones RN,Baud MG,Wilcken R,Boeckler FM,Fersht AR,Joerger AC,Spencer J

    更新日期：2016-08-19 00:00:00

  • Toolbox of Diverse Linkers for Navigating the Cellular Efficacy Landscape of Stapled Peptides.

    abstract：:Stapled peptides have great potential as modulators of protein-protein interactions (PPIs). However, there is a vast landscape of chemical features that can be varied for any given peptide, and identifying a set of features that maximizes cellular uptake and subsequent target engagement remains a key challenge. Herein...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00063

    authors： Wu Y,Kaur A,Fowler E,Wiedmann MM,Young R,Galloway WRJD,Olsen L,Sore HF,Chattopadhyay A,Kwan TT,Xu W,Walsh SJ,de Andrade P,Janecek M,Arumugam S,Itzhaki LS,Lau YH,Spring DR

    更新日期：2019-03-15 00:00:00

  • Gel electrophoresis and X-ray fluorescence: A powerful combination for the analysis of protein metal binding.

    abstract：:Understanding the complex biochemical mechanisms that underlie the regulation, toxicity, and protein binding of metal ions requires the ability to analyze the metal content of individual proteins in complex mixtures. In this issue of ACS Chemical Biology, a technique combining gel electrophoresis with synchrotron X-ra...

    journal_title：ACS chemical biology

    pub_type： 评论,杂志文章

    doi：10.1021/cb100145z

    authors： Zahler NH

    更新日期：2010-06-18 00:00:00

  • In vitro selection of anti-Akt2 thioether-macrocyclic peptides leading to isoform-selective inhibitors.

    abstract：:The Akt kinase family, consisting of three isoforms in humans, is a well-validated class of drug target. Through various screening campaigns in academics and pharmaceutical industries, several promising inhibitors have been developed to date. However, due to the mechanistic and structural similarities of Akt kinases, ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb200388k

    authors： Hayashi Y,Morimoto J,Suga H

    更新日期：2012-03-16 00:00:00

  • How ATP-Competitive Inhibitors Allosterically Modulate Tyrosine Kinases That Contain a Src-like Regulatory Architecture.

    abstract：:Small molecule kinase inhibitors that stabilize distinct ATP binding site conformations can differentially modulate the global conformation of Src-family kinases (SFKs). However, it is unclear which specific ATP binding site contacts are responsible for modulating the global conformation of SFKs and whether these inhi...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.0c00429

    authors： Fang L,Vilas-Boas J,Chakraborty S,Potter ZE,Register AC,Seeliger MA,Maly DJ

    更新日期：2020-07-17 00:00:00

  • Mechanistic Insights into Taxadiene Epoxidation by Taxadiene-5α-Hydroxylase.

    abstract：:The anticancer molecule taxol (Paclitaxel) stands as one of the most medically and economically important natural products. However, despite decades of extensive study, its biosynthesis remains poorly understood. Unpredictable behavior of the first oxygenation enzyme, taxadiene-5α-hydroxylase, which produces a range o...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00767

    authors： Edgar S,Zhou K,Qiao K,King JR,Simpson JH,Stephanopoulos G

    更新日期：2016-02-19 00:00:00

  • Parsimonious discovery of synergistic drug combinations.

    abstract：:Combination therapies that enhance efficacy or permit reduced dosages to be administered have seen great success in a variety of therapeutic applications. More fundamentally, the discovery of epistatic pathway interactions not only informs pharmacologic intervention but can be used to better understand the underlying ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb2003225

    authors： Severyn B,Liehr RA,Wolicki A,Nguyen KH,Hudak EM,Ferrer M,Caldwell JS,Hermes JD,Li J,Tudor M

    更新日期：2011-12-16 00:00:00

  • Cholesterol, it's not just for heart disease anymore.

    abstract：:Recent studies have shown that cholesterol plays a significant role in the ability of Toxin A from Clostridium difficile to enter eukaryotic cells. The translocation process is one of three major steps during intoxication that could be targeted for intervention against the severe antibiotic-associated diarrhea caused ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb600133b

    authors： Kerzmann A,Feig AL

    更新日期：2006-04-25 00:00:00

  • Quantitative analysis of T cell receptor complex interaction sites using genetically encoded photo-cross-linkers.

    abstract：:The T cell receptor (TCR)-cluster of differentiation 3 (CD3) signaling complex plays an important role in initiation of adaptive immune responses, but weak interactions have obstructed delineation of the individual TCR-CD3 subunit interactions during T cell signaling. Here, we demonstrate that unnatural amino acids (U...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb500351s

    authors： Wang W,Li T,Felsovalyi K,Chen C,Cardozo T,Krogsgaard M

    更新日期：2014-09-19 00:00:00

  • Reporter enzyme inhibitor study to aid assembly of orthogonal reporter gene assays.

    abstract：:Reporter gene assays (RGAs) are commonly used to measure biological pathway modulation by small molecules. Understanding how such compounds interact with the reporter enzyme is critical to accurately interpret RGA results. To improve our understanding of reporter enzymes and to develop optimal RGA systems, we investig...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb3007264

    authors： Ho PI,Yue K,Pandey P,Breault L,Harbinski F,McBride AJ,Webb B,Narahari J,Karassina N,Wood KV,Hill A,Auld DS

    更新日期：2013-05-17 00:00:00

  • High Throughput Screen Identifies Small Molecule Effectors That Modulate Thin Filament Activation in Cardiac Muscle.

    abstract：:Current therapeutic interventions for both heart disease and heart failure are largely insufficient and associated with undesired side effects. Biomedical research has emphasized the role of sarcomeric protein function for the normal performance and energy efficiency of the heart, suggesting that directly targeting th...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.0c00908

    authors： Parijat P,Kondacs L,Alexandrovich A,Gautel M,Cobb AJA,Kampourakis T

    更新日期：2021-01-15 00:00:00

  • Cell Permeable Ratiometric Fluorescent Sensors for Imaging Phosphoinositides.

    abstract：:Phosphoinositides are critical cell-signal mediators present on the plasma membrane. The dynamic change of phosphoinositide concentrations on the membrane including clustering and declustering mediates signal transduction. The importance of phosphoinositides is scored by the fact that they participate in almost all ce...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.6b00067

    authors： Mondal S,Rakshit A,Pal S,Datta A

    更新日期：2016-07-15 00:00:00

  • HIV-1 Env-Dependent Cell Killing by Bifunctional Small-Molecule/Peptide Conjugates.

    abstract：:A strategy has been established for the synthesis of a family of bifunctional HIV-1 inhibitor covalent conjugates with the potential to bind simultaneously to both the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein trimeric complex (Env). One component of the conjugates is derived from BNM-III-170, a small...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.0c00888

    authors： Gaffney A,Nangarlia A,Ang CG,Gossert S,Rashad Ahmed AA,Hossain MA,Abrams CF,Smith AB 3rd,Chaiken I

    更新日期：2021-01-15 00:00:00

  • Novel inhibitors of human DOPA decarboxylase extracted from Euonymus glabra Roxb.

    abstract：:Dopamine, a biogenic amine with important biological functions, is produced from l-DOPA by DOPA decarboxylase (DDC). DDC is a potential target to modulate the production of dopamine in several pathological states. Known inhibitors of DDC have been used for treatment of Parkinson's disease but suffered low specificity ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb500009r

    authors： Ren J,Zhang Y,Jin H,Yu J,Zhou Y,Wu F,Zhang W

    更新日期：2014-04-18 00:00:00

  • Functional evaluation of key interactions evident in the structure of the eukaryotic Cys-loop receptor GluCl.

    abstract：:The publication of the first high-resolution crystal structure of a eukaryotic Cys-loop receptor, GluClα, has provided valuable structural information on this important class of ligand-gated ion channels (LGIC). However, limited functional data exist for the GluCl receptors. Before applying the structural insights fro...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb500323d

    authors： Daeffler KN,Lester HA,Dougherty DA

    更新日期：2014-10-17 00:00:00

  • siRNA screen identifies the phosphatase acting on the G protein-coupled thyrotropin-releasing hormone receptor.

    abstract：:G protein-coupled receptors (GPCRs) are an ubiquitously expressed class of transmembrane proteins involved in the signal transduction of neurotransmitters, hormones and various other ligands. Their signaling output is desensitized by mechanisms involving phosphorylation, internalization, and dissociation from G protei...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb3004513

    authors： Gehret AU,Hinkle PM

    更新日期：2013-03-15 00:00:00

  • The Supersized Class III Lanthipeptide Stackepeptin Displays Motif Multiplication in the Core Peptide.

    abstract：:Lanthipeptides are ribosomally synthesized and post-translationally modified peptides bearing the characteristic amino acids lanthionine and/or labionin. Here, we report on the discovery and characterization of the stackepeptins, produced by the Actinomycete Stackebrandtia nassauensis DSM-44728(T). The stackepeptins a...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00651

    authors： Jungmann NA,van Herwerden EF,Hügelland M,Süssmuth RD

    更新日期：2016-01-15 00:00:00

  • Generation of Optogenetically Modified Adenovirus Vector for Spatiotemporally Controllable Gene Therapy.

    abstract：:Gene therapy is expected to be utilized for the treatment of various diseases. However, the spatiotemporal resolution of current gene therapy technology is not high enough. In this study, we generated a new technology for spatiotemporally controllable gene therapy. We introduced optogenetic and CRISPR/Cas9 techniques ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b01058

    authors： Takayama K,Mizuguchi H

    更新日期：2018-02-16 00:00:00

  • Molecular tweezers inhibit islet amyloid polypeptide assembly and toxicity by a new mechanism.

    abstract：:In type-2 diabetes (T2D), islet amyloid polypeptide (IAPP) self-associates into toxic assemblies causing islet β-cell death. Therefore, preventing IAPP toxicity is a promising therapeutic strategy for T2D. The molecular tweezer CLR01 is a supramolecular tool for selective complexation of K residues in (poly)peptides. ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00146

    authors： Lopes DH,Attar A,Nair G,Hayden EY,Du Z,McDaniel K,Dutt S,Bravo-Rodriguez K,Mittal S,Klärner FG,Wang C,Sanchez-Garcia E,Schrader T,Bitan G

    更新日期：2015-06-19 00:00:00

  • Peripheral protein organization and its influence on lipid diffusion in biomimetic membranes.

    abstract：:Protein organization on biomembranes and their dynamics are essential for cellular function. It is not clear, however, how protein binding may influence the assembly of underlying lipids or how the membrane structure leads to functional protein organization. Toward this goal, we investigated the effects of annexin a5 ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb900303s

    authors： Vats K,Knutson K,Hinderliter A,Sheets ED

    更新日期：2010-04-16 00:00:00

  • Turn-on Fluorene Push-Pull Probes with High Brightness and Photostability for Visualizing Lipid Order in Biomembranes.

    abstract：:The rational design of environmentally sensitive dyes with superior properties is critical for elucidating the fundamental biological processes and understanding the biophysical behavior of cell membranes. In this study, a novel group of fluorene-based push-pull probes was developed for imaging membrane lipids. The de...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00658

    authors： Shaya J,Collot M,Bénailly F,Mahmoud N,Mély Y,Michel BY,Klymchenko AS,Burger A

    更新日期：2017-12-15 00:00:00

  • Isoxazole Alters Metabolites and Gene Expression, Decreasing Proliferation and Promoting a Neuroendocrine Phenotype in β-Cells.

    abstract：:Novel strategies are needed to modulate β-cell differentiation and function as potential β-cell replacement or restorative therapies for diabetes. We previously demonstrated that small molecules based on the isoxazole scaffold drive neuroendocrine phenotypes. The nature of the effects of isoxazole compounds on β-cells...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00993

    authors： Kalwat MA,Huang Z,Wichaidit C,McGlynn K,Earnest S,Savoia C,Dioum EM,Schneider JW,Hutchison MR,Cobb MH

    更新日期：2016-04-15 00:00:00

  • Using a Specific RNA-Protein Interaction To Quench the Fluorescent RNA Spinach.

    abstract：:RNAs are involved in interaction networks with other biomolecules and are crucial for proper cell function. Yet their biochemical analysis remains challenging. For Förster Resonance Energy Transfer (FRET), a common tool to study such interaction networks, two interacting molecules have to be fluorescently labeled. "Sp...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00332

    authors： Roszyk L,Kollenda S,Hennig S

    更新日期：2017-12-15 00:00:00

  • Discovery of Novel Antibiotics as Covalent Inhibitors of Fatty Acid Synthesis.

    abstract：:The steady increase in the prevalence of multidrug-resistant Staphylococcus aureus has made the search for novel antibiotics to combat this clinically important pathogen an urgent matter. In an effort to discover antibacterials with new chemical structures and mechanisms, we performed a growth inhibition screen of a s...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00982

    authors： Wang J,Ye X,Yang X,Cai Y,Wang S,Tang J,Sachdeva M,Qian Y,Hu W,Leeds JA,Yuan Y

    更新日期：2020-07-17 00:00:00

  • A Versatile Transcription-Translation in One Approach for Activation of Cryptic Biosynthetic Gene Clusters.

    abstract：:The ever-growing drug resistance problem worldwide highlights the urgency to discover and develop new drugs. Microbial natural products are a prolific source of drugs. Genome sequencing has revealed a tremendous amount of uncharacterized natural product biosynthetic gene clusters (BGCs) encoded within microbial genome...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.0c00581

    authors： Zhang Q,Ren JW,Wang W,Zhai J,Yang J,Liu N,Huang Y,Chen Y,Pan G,Fan K

    更新日期：2020-09-18 00:00:00

  • Conformational Changes in Alkyl Chains Determine the Thermodynamic and Kinetic Binding Profiles of Carbonic Anhydrase Inhibitors.

    abstract：:Thermodynamics and kinetics of protein-ligand binding are both important aspects for the design of novel drug molecules. Presently, thermodynamic data are collected with isothermal titration calorimetry, while kinetic data are mostly derived from surface plasmon resonance. The new method of kinITC provides both thermo...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00895

    authors： Glöckner S,Ngo K,Sager CP,Hüfner-Wulsdorf T,Heine A,Klebe G

    更新日期：2020-03-20 00:00:00

  • The Role of Reactive Oxygen Species and Ferroptosis in Heme-Mediated Activation of Human Platelets.

    abstract：:Hemolysis, a process by which the destruction of red blood cells leads to the release of hemoglobin, is a critical event observed during hemolytic disorders. Under oxidative stress conditions, hemoglobin can release its heme prosthetic group, which is highly cytotoxic and can catalyze the generation of reactive oxygen...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.8b00458

    authors： NaveenKumar SK,SharathBabu BN,Hemshekhar M,Kemparaju K,Girish KS,Mugesh G

    更新日期：2018-08-17 00:00:00

  • Identification and Characterization of Dual Inhibitors of the USP25/28 Deubiquitinating Enzyme Subfamily.

    abstract：:The ubiquitin proteasome system is widely postulated to be a new and important field of drug discovery for the future, with the ubiquitin specific proteases (USPs) representing one of the more attractive target classes within the area. Many USPs have been linked to critical axes for therapeutic intervention, and the f...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00334

    authors： Wrigley JD,Gavory G,Simpson I,Preston M,Plant H,Bradley J,Goeppert AU,Rozycka E,Davies G,Walsh J,Valentine A,McClelland K,Odrzywol KE,Renshaw J,Boros J,Tart J,Leach L,Nowak T,Ward RA,Harrison T,Andrews DM

    更新日期：2017-12-15 00:00:00

  • Cyanopyrrolidine Inhibitors of Ubiquitin Specific Protease 7 Mediate Desulfhydration of the Active-Site Cysteine.

    abstract：:Ubiquitin specific protease 7 (USP7) regulates the protein stability of key cellular regulators in pathways ranging from apoptosis to neuronal development, making it a promising therapeutic target. Here we used an engineered, activated variant of the USP7 catalytic domain to perform structure-activity studies of elect...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.0c00031

    authors： Bashore C,Jaishankar P,Skelton NJ,Fuhrmann J,Hearn BR,Liu PS,Renslo AR,Dueber EC

    更新日期：2020-06-19 00:00:00