Abstract：
:Cells respond to stress by controlling gene expression at several levels, with little known about the role of translation. Here, we demonstrate a coordinated translational stress response system involving stress-specific reprogramming of tRNA wobble modifications that leads to selective translation of codon-biased mRNAs representing different classes of critical response proteins. In budding yeast exposed to four oxidants and five alkylating agents, tRNA modification patterns accurately distinguished among chemically similar stressors, with 14 modified ribonucleosides forming the basis for a data-driven model that predicts toxicant chemistry with >80% sensitivity and specificity. tRNA modification subpatterns also distinguish SN1 from SN2 alkylating agents, with SN2-induced increases in m(3)C in tRNA mechanistically linked to selective translation of threonine-rich membrane proteins from genes enriched with ACC and ACT degenerate codons for threonine. These results establish tRNA modifications as predictive biomarkers of exposure and illustrate a novel regulatory mechanism for translational control of cell stress response.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Chan CT,Deng W,Li F,DeMott MS,Babu IR,Begley TJ,Dedon PCdoi
10.1021/acs.chemrestox.5b00004subject
Has Abstractpub_date
2015-05-18 00:00:00pages
978-88issue
5eissn
0893-228Xissn
1520-5010journal_volume
28pub_type
杂志文章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
更新日期：2001-05-01 00:00:00
abstract：:Mitomycin C (MMC) is a genotoxic cancer chemotherapeutic agent that reacts principally at the N2 position of guanine to form one of two predominant monoadducts, or a G-G interstrand cross-link at CpG sites, or a G-G intrastrand cross-link at GpG sites. Previous studies of MMC adduction have principally used very short...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx960070c
更新日期：1996-10-01 00:00:00
abstract：:Dysregulation in the expression of microRNAs (miRNAs), single-stranded RNAs which regulate gene expression, has been associated with diseases such as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), although their cellular origin has not been explored. Thus, the focus of this work was to study expressi...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.7b00330
更新日期：2018-06-18 00:00:00
abstract：:The carcinogen 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) alkylates DNA at dGuo, dAdo, and dCyd. dCyd adducts, formed in small amounts, elute near the more abundant dGuo adducts. We isolated the dCyd adducts formed with dCMP. Each BPDE enantiomer forms three major adducts with dCMP, two...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0340201
更新日期：2004-04-01 00:00:00
abstract：:The seaweed Fucus vesiculosus is unusual when compared with other algal species, in that it can survive in toxic-metal-contaminated aquatic environments. The metallothionein gene has been identified in F. vesiculosus by Kille and co-workers (Morris, C. A., Nicolaus, B., Sampson, V., Harwood, J. L., and Kille, P. (1999...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx050206j
更新日期：2006-03-01 00:00:00
abstract：:N'-Nitrosonornicotine (NNN) and N-nitrosopiperidine (NPIP) are potent esophageal and nasal cavity carcinogens in rats and pulmonary carcinogens in mice. N-Nitrosopyrrolidine (NPYR) induces mainly liver tumors in rats and is a weak pulmonary carcinogen in mice. These nitrosamines may be causative agents in human cancer...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0497696
更新日期：2005-01-01 00:00:00
abstract：:Polychlorinated biphenyls (PCBs) are one of the most refractory environmental pollutants. Because of their ubiquitous existence in the biological systems (including human body), it is important to investigate their toxic behavior. Our previous findings demonstrated that a high reactive metabolite of PCB, namely PCB29-...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.8b00376
更新日期：2019-06-17 00:00:00
abstract：:Faithful replication of DNA is a critical aspect in maintaining genome integrity. DNA polymerases are responsible for replicating DNA, and high-fidelity polymerases do this rapidly and at low error rates. Upon exposure to exogenous or endogenous substances, DNA can become damaged and this can alter the speed and fidel...
journal_title：Chemical research in toxicology
pub_type： 杂志文章,评审
doi：10.1021/acs.chemrestox.7b00224
更新日期：2017-11-20 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx300259x
更新日期：2012-08-20 00:00:00
abstract：:Available studies, while limited in number, suggest that e-cigarette vaping induces oxidative stress, with one potential mechanism being the direct formation of reactive oxygen species (ROS) in e-vapor. In the present studies, we measured the formation of hydroxyl radical (•OH), the most destructive ROS, in e-vapor un...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.8b00400
更新日期：2019-06-17 00:00:00
abstract：:Electronic cigarette liquids (e-liquids) with sweetener additives such as sucralose, a synthetic chlorinated disaccharide, are popular among some e-cigarette consumers; sucralose can be added either by the manufacturer or by the consumer. The prevalence of sucralose in commercial e-liquids is not known, nor is the typ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.9b00047
更新日期：2019-06-17 00:00:00
abstract：:A series of (alkylthio)trifluoropropanones containing a heterocyclic moiety was synthesized. The compounds were tested for in vitro inhibition of four hydrolytic enzymes including insect juvenile hormone esterase (JHE), eel acetylcholinesterase (AChE), yeast lipase (LP), and bovine alpha-chymotrypsin. The I50 values r...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00016a009
更新日期：1990-07-01 00:00:00
abstract：:Green tea catechins and hydrolyzable tannins are gaining increasing attention as chemopreventive agents. However, their mechanism of action is poorly understood. We investigated the effects of four green tea catechins and two hydrolyzable tannins on microsome-induced benzo[a]pyrene (BP)-DNA adducts and the possible st...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx900412a
更新日期：2010-04-19 00:00:00
abstract：:Many herbal medicines such as epimedium have been reported to cause adverse effects, and icaritin is the common aglycone of many glucosides in epimedium. Our present work aimed at the clarification of the metabolic activation of icaritin possibly responsible for the adverse effects of epimedium. A quinone methide meta...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.8b00418
更新日期：2019-06-17 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.8b00371
更新日期：2019-04-15 00:00:00
abstract：:Acyl glucuronides (AGs) are reactive metabolites of carboxylic acid-containing drugs, which are associated with idiosyncratic toxicity (IDT) such as anaphylaxis, drug-induced liver injury, and so on. In this study, we developed a new in vitro approach for the quantitative assessment of the reactivity of AGs and their ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.9b00111
更新日期：2019-10-21 00:00:00
abstract：:The deamination of DNA bases by three alpha-nitrosaminoaldehydes, butylethanalnitrosamine, methylethanalnitrosamine, and N-nitroso-2-hydroxymorpholine (NHMOR), the direct metabolite of potent animal carcinogen N-nitrosodiethanolamine, was demonstrated by a set of in vitro experiments. The deamination of guanine, adeni...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx990126d
更新日期：2000-02-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
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更新日期：1999-10-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
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更新日期：2003-10-01 00:00:00
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更新日期：2010-06-21 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0341456
更新日期：2004-03-01 00:00:00
abstract：:Chemical respiratory sensitization is an immunological process that manifests clinically mostly as occupational asthma and is responsible for 1 in 6 cases of adult asthma, although this may be an underestimate of the prevalence, as it is under-diagnosed. Occupational asthma results in unemployment for roughly one-thir...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.0c00320
更新日期：2020-12-15 00:00:00
abstract：:Notopterygium forbesii Boiss (NF) has been used as a traditional Chinese medicine for the treatment of common cold and rheumatism. However, there has been limited research on the biological properties of NF, and the mechanisms of action remain unknown. Here, we aimed to study the mechanism of NF-induced heme oxygenase...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx800301f
更新日期：2008-12-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.9b00382
更新日期：2020-06-15 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.9b00171
更新日期：2019-06-17 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
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更新日期：2013-03-18 00:00:00
abstract：:p,p'-DDE, the main metabolite of DDT, is notorious for its persistent and bioaccumulation. It has detrimental effects on the nervous system, while the mechanism is unclear. We sought to investigate the mechanism of p,p'-DDE-induced neurocytic apoptosis in PC12 cells by cytoflow and screen the potential target gene by ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx4003963
更新日期：2014-04-21 00:00:00
abstract：:We report on the generation of computer-based models for the prediction of the chromosome-damaging potential of chemicals as assessed in the in vitro chromosome aberration (CA) test. On the basis of publicly available CA-test results of more than 650 chemical substances, half of which are drug-like compounds, we gener...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx060136w
更新日期：2006-10-01 00:00:00
abstract：:The toxic alpha,beta-unsaturated aldehyde acrolein readily attacks proteins, generating adducts at cysteine, histidine, and lysine residues. In this study, rabbit antiserum was raised against acrolein-modified keyhole limpet hemocyanin in the expectation that it would allow immunodetection of adducted proteins in biol...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0341106
更新日期：2003-10-01 00:00:00
