Abstract：
:To prevent the accumulation of reactive oxygen species and limit associated damage to biological macromolecules, cells express a variety of oxidant-detoxifying enzymes, including peroxiredoxins. In Saccharomyces cerevisiae, the peroxiredoxin Tsa1 plays a key role in peroxide clearance and maintenance of genome stability. Five homodimers of Tsa1 can assemble into a toroid-shaped decamer, with the active sites in the enzyme being shared between individual dimers in the decamer. Here, we have examined whether two conserved aromatic residues at the decamer-building interface promote Tsa1 oligomerization, enzymatic activity, and biological function. When substituting either or both of these aromatic residues at the decamer-building interface with either alanine or leucine, we found that the Tsa1 decamer is destabilized, favoring dimeric species instead. These proteins exhibit varying abilities to rescue the phenotypes of oxidant sensitivity and genomic instability in yeast lacking Tsa1 and Tsa2, with the individual leucine substitutions at this interface partially complementing the deletion phenotypes. The ability of Tsa1 decamer interface variants to partially rescue peroxidase function in deletion strains is temperature-dependent and correlates with their relative rate of reactivity with hydrogen peroxide and their ability to interact with thioredoxin. Based on the combined results of in vitro and in vivo assays, our findings indicate that multiple steps in the catalytic cycle of Tsa1 may be impaired by introducing substitutions at its decamer-building interface, suggesting a multifaceted biological basis for its assembly into decamers.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Loberg MA,Hurtig JE,Graff AH,Allan KM,Buchan JA,Spencer MK,Kelly JE,Clodfelter JE,Morano KA,Lowther WT,West JDdoi
10.1021/acs.chemrestox.8b00346subject
Has Abstractpub_date
2019-03-18 00:00:00pages
474-483issue
3eissn
0893-228Xissn
1520-5010journal_volume
32pub_type
杂志文章abstract：:1-Hydroxypyrene (HOP), a metabolite found in the urine of humans and laboratory animals exposed to polycyclic aromatic hydrocarbons (PAHs), is known to be both acutely toxic and genotoxic. It has been widely used as a biomarker for studying PAH exposure. In this research, we have found that, upon UVA irradiation, HOP ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx990199x
更新日期：2000-07-01 00:00:00
abstract：:The PI3K/Akt/mTOR pathway is considered to be an attractive target for the development of novel anticancer molecules. This paper reports for the first time that a small molecule, antrocin (MW = 234), from Antrodia camphorata was a potent antagonist in various cancer types, being highest in metastatic breast cancer MDA...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx100318m
更新日期：2011-02-18 00:00:00
abstract：:Exposure to arsenic affects large human populations worldwide and has been associated with a long list of human diseases, including skin, bladder, lung, and liver cancers, diabetes, and cardiovascular disorders. In addition, there are large individual differences in susceptibility to arsenic-induced diseases, which ar...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx4002868
更新日期：2013-12-16 00:00:00
abstract：:The crystal structure of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) has been determined by single-crystal X-ray crystallography. Crystals grown by evaporation of an aqueous solution form in the monoclinic space group P2(1)/n with two molecules of PhIP per asymmetric unit, along with six w...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx950168b
更新日期：1996-04-01 00:00:00
abstract：:Drug-induced kidney injury (DIKI) is a common toxicity observed in pharmaceutical development. We demonstrated the use of label-free liquid chromatography-mass spectrometry (LC-MS) and multiplex liquid chromatography-single reaction monitoring (LC-SRM) as practical extensions of standard immunoassay based safety bioma...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.7b00159
更新日期：2017-10-16 00:00:00
abstract：:Metabolic pathways of the mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) remain incompletely characterized in humans. In this study, the metabolism of MeIQx was investigated in primary human hepatocytes. Six metabolites were characterized by UV and mass spectroscopy. Novel metabolites were additionally ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx000176e
更新日期：2001-02-01 00:00:00
abstract：:Nevirapine (NVP) treatment is associated with a significant incidence of skin rash in humans, and it also causes a similar immune-mediated skin rash in Brown Norway (BN) rats. We have shown that the sulfate of a major oxidative metabolite, 12-OH-NVP, covalently binds in the skin. The fact that the sulfate metabolite i...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx400098z
更新日期：2013-05-20 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：:The effect of adduct stereochemistry on the susceptibility to hydrolysis by snake venom (VPD) and bovine spleen (SPD) phosphodiesterases was investigated with short deoxyoligonucleotides containing defined adducts derived from alkylation of the exocyclic 6-amino group of dA by polycyclic aromatic hydrocarbon diol epox...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx010092l
更新日期：2001-09-01 00:00:00
abstract：:Acrolein is a highly toxic environmental pollutant that readily alkylates the epsilon-amino group of lysine residues in proteins. In model systems, such chemistry involves sequential addition of two acrolein molecules to a given nitrogen, forming bis-Michael-adducted species that undergo aldol condensation and dehydra...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0502387
更新日期：2005-11-01 00:00:00
abstract：:Hydroxyl radical can be induced from Fenton reaction or gamma radiolysis of water. It can add preferentially to the C5 position of thymidine to give the 5-hydroxy-5,6-dihydrothymidin-6-yl radical. In this report, we examined the independent generation and reactivity of this radical in oligodeoxyribonucleotides (ODNs)....
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx050195u
更新日期：2005-12-01 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：:To obtain definitive information about the mechanisms of urinary calculus formation and the structural characteristics of the calculi induced by biphenyl administration in rats, with a focus on the sex dependency, the constituents of the urinary calculi were analyzed by HPLC, inductively coupled plasma spectroscopy (I...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0000163
更新日期：2000-08-01 00:00:00
abstract：:The conformation of the crotonaldehyde-derived N(2)-[3-oxo-1(S)-methyl-propyl]-dG adduct in the oligodeoxynucleotide 5'-d(G(1)C(2)T(3)A(4)G(5)C(6)X(7)A(8)G(9)T(10)C(11)C(12))-3'.5'-d(G(13)G(14)A(15)C(16)T(17)C(18)G(19)C(20)T(21)A(22)G(23)C(2)(4))-3', where X = N(2)-[3-oxo-1(S)-methyl-propyl]-dG, is reported. This addu...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0600604
更新日期：2006-08-01 00:00:00
abstract：:In recent years, there has been an increase in the production of shellfish and in global demand for seafood as nutritious and healthy food. Unfortunately, a significant number of incidences of shellfish poisoning occur worldwide, and microalgae that produce phycotoxins are responsible for most of these. Phycotoxins in...
journal_title：Chemical research in toxicology
pub_type： 杂志文章,评审
doi：10.1021/tx200182m
更新日期：2011-11-21 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：: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
更新日期：2003-12-01 00:00:00
abstract：:Idiosyncratic drug reactions (IDRs) represent a major clinical problem, and at present, the mechanisms involved are still poorly understood. One animal model that we have used for mechanistic studies of IDRs is penicillamine-induced autoimmunity in Brown Norway (BN) rats. Previous work in our lab found that macrophage...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx900087z
更新日期：2009-07-01 00:00:00
abstract：:The reaction of chromium(VI) with hydrogen peroxide was studied in the presence of glutathione. In vitro, reaction of chromium(VI) with hydrogen peroxide alone led to production of hydroxyl radical as the significant reactive intermediate, while reaction of chromium(VI) with glutathione led to formation of two chromiu...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00018a016
更新日期：1990-11-01 00:00:00
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
更新日期：1996-06-01 00:00:00
abstract：:Protein-xenobiotic adducts are byproducts of xenobiotic metabolism. While there is a correlation between protein adduction and target organ toxicity, a cause and effect relationship is not often clear. Naphthoquinone (NQ) and monocrotaline pyrrole (MCTP) are two pneumotoxic electrophiles that form covalent adducts wit...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx1002436
更新日期：2010-09-20 00:00:00
abstract：:Bisphenol A (BPA) is ubiquitous in the environment and is reported to be present at high concentrations in placental tissue, where its presence raises concerns over its potential to disrupt placental function. This report investigates how BPA interferes with the survival of human choriocarcinoma BeWo cells (a model of...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.5b00093
更新日期：2015-09-21 00:00:00
abstract：:One possible mechanism linking inflammation with cancer involves the generation of reactive oxygen, nitrogen, and halogen species by activated macrophages and neutrophils infiltrating sites of infection or tissue damage, with these chemical mediators causing damage that ultimately leads to cell death and mutation. To ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx300473n
更新日期：2013-04-15 00:00:00
abstract：:Because of the association between inhalation of airborne particulate matter (PM) and human respiratory and cardiovascular disease, it is necessary to understand the tissue damage induced by these particles. One of the cell types principally involved in the body's reaction to PM are macrophages, which remove particles...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx034118f
更新日期：2004-01-01 00:00:00
abstract：:Methylmercury (MeHg) reacts readily with GSH, leading to the formation of a MeHg-SG adduct that is excreted into extracellular space through multidrug-resistance-associated protein (MRP), which is regulated by the transcription factor Nrf2. We previously reported that MeHg covalently modifies Keap1 and activates Nrf2 ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx5002332
更新日期：2014-10-20 00:00:00
abstract：:Ochratoxin A (OTA) is a mycotoxin that shows potent nephrotoxicity and renal carcinogenicity in rodents. One hypothesis for OTA-induced tumor formation is based on its genotoxic properties that are promoted by oxidative metabolism. Like other chlorinated phenols, OTA undergoes an oxidative dechlorination process to ge...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx060138g
更新日期：2006-09-01 00:00:00
abstract：:Polyunsaturated fatty acids (PUFA) are primary targets of free radical damage during oxidative stress. Diffusible electrophilic alpha,beta-unsaturated aldehydes, such as 4-hydroxynonenal (HNE), have been shown to modify proteins that mediate cell signaling (e.g., IKK and Keap1) and alter gene expression pathways respo...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx700347w
更新日期：2008-02-01 00:00:00
abstract：:Mitomycin C (MC), a cytotoxic anticancer drug and bifunctional DNA DNA alkylating agent, induces cross-linking of the complementary strands of DNA. The DNA interstrand cross-links (ICLs) are thought to be the critical cytotoxic lesions produced by MC. Decarbamoyl mitomycin C (DMC) has been regarded as a monofunctional...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx020044g
更新日期：2002-11-01 00:00:00
abstract：:The Adverse Outcome Pathway (AOP) paradigm details the existing knowledge that links the initial interaction between a chemical and a biological system, termed the molecular initiating event (MIE), through a series of intermediate events, to an adverse effect. An important example of a well-defined MIE is the formatio...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.6b00099
更新日期：2016-06-20 00:00:00
abstract：:Previously, we identified two distinct metabonomic phenotypes in Sprague-Dawley rats sourced from two different rooms (colonies) in the Charles River, Raleigh facility [Robosky, L. C., Wells, D. F., Egnash, L. A., Manning, M. L., Reily, M. D., and Robertson, D. G. (2005) Metabonomic identification of two distinct phen...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx700184u
更新日期：2007-10-01 00:00:00
