当前位置： SCI文献检索 > CHEMICAL RESEARCH IN TOXICOLOGY期刊下所有文献 > Cytochrome P450 2A5 constitutive expression and induction by heavy metals is dependent on redox-sensitive transcription factor Nrf2 in liver.

Cytochrome P450 2A5 constitutive expression and induction by heavy metals is dependent on redox-sensitive transcription factor Nrf2 in liver.

Abstract：

:Mouse cytochrome P450 2A5 (CYP2A5) is upregulated in various pathophysiological liver diseases and induced by structurally variable hepatotoxic chemicals. A putative common feature for all of these conditions is altered cellular redox status. Nuclear factor erythroid 2-like 2 (Nrf2) is a transcription factor that is post-translationally regulated by oxidative stress and controls the transcription of numerous protective target genes. In the present study, we have extensively characterized the regulation of Cyp2a5 by Nrf2 and compared it to a well-characterized target gene Hmox1. The treatment of mouse primary hepatocytes with lead chloride, methylmercury chloride, or phenethyl isothiocyanate all leads to nuclear accumulation of Nrf2. Both CYP2A5 and HMOX1 were induced by all three compounds; however, HMOX1 responded more rapidly and transiently as compared to CYP2A5. Experiments in Nrf2(-/-) primary hepatocytes showed that Nrf2 is crucial for CYP2A5 induction but not for elevation of HMOX1. Both CYP2A5 and HMOX1 were upregulated by Nrf2 overexpression and downregulated by Keap1 or Bach1 overexpression. However, in all cases, CYP2A5 responded much more potently. Results in Nrf2-deficient animals showed that CYP2A5 expression is significantly attenuated in the absence of Nrf2, while expression of HMOX1 was unaffected. Therefore, Cyp2a5 joins the group of genes constitutively regulated by Nrf2. Our current results unequivocally show that expression of CYP2A5 is tightly controlled by Nrf2 in liver. Nrf2 is needed for constitutive expression of CYP2A5, and CYP2A5 is also sensitively upregulated by an increased level of Nrf2 protein. Therefore, CYP2A5 upregulation could be a useful indicator for hepatic activation of the Nrf2 pathway.

journal_name

Chem Res Toxicol

journal_title

Chemical research in toxicology

authors

Lämsä V,Levonen AL,Leinonen H,Ylä-Herttuala S,Yamamoto M,Hakkola J

doi

10.1021/tx100084c

subject

Has Abstract

pub_date

2010-05-17 00:00:00

pages

977-85

issue

5

eissn

0893-228X

issn

1520-5010

journal_volume

23

pub_type

杂志文章

相关文献

CHEMICAL RESEARCH IN TOXICOLOGY文献大全
  • Fatty Acid Remodeling of Membrane Glycerophospholipids Induced by Bleomycin and Iron Oxide Nanoparticles in Human Embryonic Kidney Cells.

    abstract：:Bleomycin has a long-studied mechanism of action through the formation of a complex with metals, such as iron. The bleomycin-iron complex was recently shown to induce membrane damage by free radical reactivity. Because the use of Fe nanoparticles is spreading for drug delivery strategies, molecular mechanisms of cell ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.0c00162

    authors： Krokidis MG,Louka M,Efthimiadou EK,Ferreri C,Chatgilialoglu C

    更新日期：2020-10-19 00:00:00

  • Studies on the adduct heterogeneity of benzo[a]pyrene 7, 8-dihydrodiol 9,10-epoxide stereoisomers covalently bound to deoxyribooligonucleotides by induced circular dichroism and light absorption spectroscopy.

    abstract：:The binding conformations of single anti- and syn-BPDE-N2-dG adducts in oligonucleotides of varying base composition have been studied by induced circular dichroism (ICD) and light absorption spectroscopy. The sign of the ICD in single-stranded oligonucleotide adducts correlates with the absolute configuration of the ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx9702244

    authors： Pradhan P,Jernström B,Seidel A,Nordén B,Gräslund A

    更新日期：1999-05-01 00:00:00

  • Chronic Cocaine Use Causes Changes in the Striatal Proteome Depending on the Endogenous Expression of Pleiotrophin.

    abstract：:The neurotrophic factor pleiotrophin (PTN) is upregulated in different brain areas after the administration of different drugs of abuse, including psychostimulants. PTN has been shown to prevent cocaine-induced cytotoxicity in NG108-15 and PC12 cells. We previously demonstrated that specific phosphoproteins related to...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.5b00130

    authors： Vicente-Rodríguez M,Herradón G,Ferrer-Alcón M,Uribarri M,Pérez-García C

    更新日期：2015-07-20 00:00:00

  • A new role for glutathione: protection of vitamin B12 from depletion by xenobiotics.

    abstract：:NADPH in microsomes reduces the hydroxocob(III)alamin form of vitamin B12 to cob(II)alamin and the supernucleophilic cob(I)alamin, which are both highly reactive toward xenobiotic epoxides formed by mammalian metabolism of dienes such as the industrially important chemicals chloroprene and 1,3-butadiene. With styrene,...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx0497898

    authors： Watson WP,Munter T,Golding BT

    更新日期：2004-12-01 00:00:00

  • Comparison of rates of enzymatic oxidation of aflatoxin B1, aflatoxin G1, and sterigmatocystin and activities of the epoxides in forming guanyl-N7 adducts and inducing different genetic responses.

    abstract：:The genotoxicity of the dihydrofurans aflatoxin B1 (AFB1), aflatoxin G1 (AFG1), and sterigmatocystin (STG) was examined in a bacterial system in which the induction of SOS repair is monitored with the umuC gene linked to a lacZ reporter gene in plasmid pSK1002. Human liver microsomal cytochrome P-450NF oxidized the di...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx00008a008

    authors： Baertschi SW,Raney KD,Shimada T,Harris TM,Guengerich FP

    更新日期：1989-03-01 00:00:00

  • Neuroprotection in the MPTP Parkinsonian C57BL/6 mouse model by a compound isolated from tobacco.

    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

    authors： Castagnoli KP,Steyn SJ,Petzer JP,Van der Schyf CJ,Castagnoli N Jr

    更新日期：2001-05-01 00:00:00

  • Reductive activation of mitomycin C by thiols: kinetics, mechanism, and biological implications.

    abstract：:The clinically used antitumor antibiotic mitomycin C requires a reductive activation to be converted to a bis-electrophile that forms several covalent adducts with DNA, including an interstrand cross-link which is considered to be the lesion responsible for the cytotoxic effects of the drug. Enzymes such as cytochrome...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx9002758

    authors： Paz MM

    更新日期：2009-10-01 00:00:00

  • Development of a thyroperoxidase inhibition assay for high-throughput screening.

    abstract：:High-throughput screening (HTPS) assays to detect inhibitors of thyroperoxidase (TPO), the enzymatic catalyst for thyroid hormone (TH) synthesis, are not currently available. Herein, we describe the development of a HTPS TPO inhibition assay. Rat thyroid microsomes and a fluorescent peroxidase substrate, Amplex UltraR...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx400310w

    authors： Paul KB,Hedge JM,Rotroff DM,Hornung MW,Crofton KM,Simmons SO

    更新日期：2014-03-17 00:00:00

  • Quartz Disrupts Iron Homeostasis in Alveolar Macrophages To Impact a Pro-Inflammatory Effect.

    abstract：:The biological response of bronchial epithelial cells to particles is associated with a sequestration of cell metal by the particle surface and a subsequent disruption in host iron homeostasis. The macrophage is the cell type resident in the respiratory tract that is most likely to make initial contact with inhaled pa...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.8b00301

    authors： Ghio AJ,Soukup JM,Stonehuerner J,Tong H,Richards J,Gilmour MI,Madden MC,Shen Z,Kantrow SP

    更新日期：2019-09-16 00:00:00

  • Metabonomic evaluation of Schaedler altered microflora rats.

    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

    authors： Rohde CM,Wells DF,Robosky LC,Manning ML,Clifford CB,Reily MD,Robertson DG

    更新日期：2007-10-01 00:00:00

  • Gut microbiome perturbations induced by bacterial infection affect arsenic biotransformation.

    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

    authors： Lu K,Cable PH,Abo RP,Ru H,Graffam ME,Schlieper KA,Parry NM,Levine S,Bodnar WM,Wishnok JS,Styblo M,Swenberg JA,Fox JG,Tannenbaum SR

    更新日期：2013-12-16 00:00:00

  • Discovery of carboxyethylpyrroles (CEPs): critical insights into AMD, autism, cancer, and wound healing from basic research on the chemistry of oxidized phospholipids.

    abstract：:Basic research, exploring the hypothesis that 2-(ω-carboxyethyl)pyrrole (CEP) modifications of proteins are generated nonenzymatically in vivo is delivering a bonanza of molecular mechanistic insights into age-related macular degeneration, autism, cancer, and wound healing. CEPs are produced through covalent modificat...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章,评审

    doi：10.1021/tx200206v

    authors： Salomon RG,Hong L,Hollyfield JG

    更新日期：2011-11-21 00:00:00

  • Mass spectrometric characterization of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine N-oxidized metabolites bound at Cys34 of human serum albumin.

    abstract：:2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic aromatic amine that is formed during the cooking of meats and poultry. PhIP is a carcinogen in rodents and a potential human carcinogen. Several short-term biomarkers of PhIP have been established for human biomonitoring, but validated long-term ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx2003504

    authors： Peng L,Turesky RJ

    更新日期：2011-11-21 00:00:00

  • Limited reactivity of formyl chloride with glutathione and relevance to metabolism and toxicity of dichloromethane.

    abstract：:Formyl chloride has been indirectly implicated as an intermediate in the oxidation of CH(2)Cl(2) and proposed to be a product of the oxidation of some other compounds. Formyl chloride was synthesized and added to aqueous solutions, with CO formed as a product. The presence of glutathione (GSH) did not reduce the yield...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx060087n

    authors： Watanabe K,Guengerich FP

    更新日期：2006-08-01 00:00:00

  • Mechanistic Insights into the Cytotoxicity of Graphene Oxide Derivatives in Mammalian Cells.

    abstract：:Graphene oxide derivatives (GODs) have superb physical/chemical properties with promise for applications in biomedicine. Shape, size, and chemistry of the GODs are identified as the key parameters that impact any biological system. In this work, the GODs with a wide range of shapes (sheets, helical/longitudinal ribbon...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.9b00391

    authors： Lu P,Zehtab Yazdi A,Han XX,Al Husaini K,Haime J,Waye N,Chen P

    更新日期：2020-09-21 00:00:00

  • Action-at-a-distance mutagenesis induced by oxidized guanine in Werner syndrome protein-reduced human cells.

    abstract：:8-Oxo-7,8-dihydroguanine (G(O), 8-hydroxyguanine) in DNA is one of the most important oxidatively damaged bases and causes G:C → T:A substitution mutations. The Werner syndrome protein (WRN) is a cancer-related RecQ DNA helicase and plays many roles in DNA replication and repair. To examine the relationships between G...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx500418m

    authors： Kamiya H,Yamazaki D,Nakamura E,Makino T,Kobayashi M,Matsuoka I,Harashima H

    更新日期：2015-04-20 00:00:00

  • (-)-Epigallocatechin gallate, a major constituent of green tea, poisons human type II topoisomerases.

    abstract：:(-)-Epigallocatechin gallate (EGCG) is the most abundant and biologically active polyphenol in green tea, and many of the therapeutic benefits of the beverage have been attributed to this compound. High concentrations of EGCG are cytotoxic and trigger genotoxic events in mammalian cells. Although this catechin affects...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx700434v

    authors： Bandele OJ,Osheroff N

    更新日期：2008-04-01 00:00:00

  • Formation and structure of cross-linking and monomeric pyrrole autoxidation products in 2,5-hexanedione-treated amino acids, peptides, and protein.

    abstract：:2,5-Hexanedione (2,5-HD) is the neurotoxic gamma-diketone metabolite of the industrial solvent n-hexane. Substantial evidence indicates that 2,5-HD reacts with neurofilament protein lysine epsilon-amines to yield 2,5-dimethylpyrrole adducts and that this reaction is critical to the mechanism of toxicity. Alkylpyrroles...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx00040a011

    authors： Zhu M,Spink DC,Yan B,Bank S,DeCaprio AP

    更新日期：1994-07-01 00:00:00

  • Lauric acid as a model substrate for the simultaneous determination of cytochrome P450 2E1 and 4A in hepatic microsomes.

    abstract：:In vitro techniques have been utilized to investigate the microsomal enzymes involved in the metabolism of lauric acid and to establish conditions in which it can be used as a model substrate for both cytochrome P450 4A and cytochrome P450 2E1 in human liver microsomes. Studies of enzyme kinetics of lauric acid omega-...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx00042a018

    authors： Clarke SE,Baldwin SJ,Bloomer JC,Ayrton AD,Sozio RS,Chenery RJ

    更新日期：1994-11-01 00:00:00

  • Reduced Transcriptomic Approach for Screening and Prediction of Chemical Toxicity.

    abstract：:The reduced transcriptomic approach allows full dose range testing of hundreds of chemicals or mixtures using human cells or zebrafish embryos. Points of departure of genes and pathways can be used for potency ranking and to classify chemicals by disrupted biological pathways. ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.8b00104

    authors： Dai J

    更新日期：2018-07-16 00:00:00

  • Reactions of the Zn Proteome with Cd2+ and Other Xenobiotics: Trafficking and Toxicity.

    abstract：:Understanding the molecular basis of inorganic chemical toxicity has lagged behind the proliferation of detailed mechanisms that explain the biochemical toxicology of many organic xenobiotics. In this perspective, general barriers to explicating the bioinorganic chemistry of toxic metals are considered, followed by a ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.6b00328

    authors： Petering DH

    更新日期：2017-01-17 00:00:00

  • 12-OH-nevirapine sulfate, formed in the skin, is responsible for nevirapine-induced skin rash.

    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

    authors： Sharma AM,Novalen M,Tanino T,Uetrecht JP

    更新日期：2013-05-20 00:00:00

  • Comparison of Free Radical Levels in the Aerosol from Conventional Cigarettes, Electronic Cigarettes, and Heat-Not-Burn Tobacco Products.

    abstract：:Aerosols from electronic cigarettes and heat-not-burn tobacco products have been found to contain lower levels of almost all compounds from the list of Harmful and Potentially Harmful Constituents known to be present in tobacco products and tobacco smoke than smoke from conventional cigarettes. Free radicals, which al...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.9b00085

    authors： Shein M,Jeschke G

    更新日期：2019-06-17 00:00:00

  • Mechanism-based inactivation of human cytochromes p450s: experimental characterization, reactive intermediates, and clinical implications.

    abstract：:The P450 type cytochromes are responsible for the metabolism of a wide variety of xenobiotics and endogenous compounds. Although P450-catalyzed reactions are generally thought to lead to detoxication of xenobiotics, the reactions can also produce reactive intermediates that can react with cellular macromolecules leadi...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章,评审

    doi：10.1021/tx7002504

    authors： Hollenberg PF,Kent UM,Bumpus NN

    更新日期：2008-01-01 00:00:00

  • Inactivation of rat hepatic cytochrome P-450 isozymes by 3,5-dicarbethoxy- 2,6-dimethyl-4-ethyl-1,4-dihydropyridine.

    abstract：:We have reported [Correia et al. (1987) Arch. Biochem. Biophys. 258, 436-443] that administration of 3,5-dicarbethoxy-4-ethyl-2,6-dimethyl-1,4-dihydropyridine (DDEP) to untreated, phenobarbital (PB) pretreated, or dexamethasone (DEX) pretreated rats results in relatively selective inactivation of cytochrome P-450 (P-4...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx00012a008

    authors： Sugiyama K,Yao K,Rettie AE,Correia MA

    更新日期：1989-11-01 00:00:00

  • Common E-Cigarette Flavoring Chemicals Impair Neutrophil Phagocytosis and Oxidative Burst.

    abstract：:E-cigarette flavorings have not been thoroughly evaluated for inhalational toxicity. We have shown that the flavoring chemical cinnamaldehyde impairs human neutrophils, macrophages, and natural killer cells. Here we investigated the effects of other common e-liquid flavoring chemicals on phagocytosis and oxidative bur...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.9b00171

    authors： Hickman E,Herrera CA,Jaspers I

    更新日期：2019-06-17 00:00:00

  • The greater reactivity of estradiol-3,4-quinone vs estradiol-2,3-quinone with DNA in the formation of depurinating adducts: implications for tumor-initiating activity.

    abstract：:Strong evidence supports the idea that specific metabolites of estrogens, mainly catechol estrogen-3,4-quinones, can react with DNA to become endogenous initiators of breast, prostate, and other human cancers. Oxidation of the catechol estrogen metabolites 4-hydroxyestradiol (4-OHE2) and 2-OHE2 leads to the quinones, ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx050229y

    authors： Zahid M,Kohli E,Saeed M,Rogan E,Cavalieri E

    更新日期：2006-01-01 00:00:00

  • Structure of an Unusual Tetracyclic Deoxyguanosine Adduct: Implications for Frameshift Mutagenicity of ortho-Cyano Nitroanilines.

    abstract：:Nitroaromatic compounds represent a major class of industrial chemicals that are also found in nature. Polycyclic derivatives are regarded as potent mutagens and carcinogens following bioactivation to produce nitrenium electrophiles that covalently modify DNA to afford N-linked C8-2'-deoxyguanosine (C8-dG) lesions tha...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.9b00411

    authors： Manning TW,Al-Abdul-Wahid MS,Manderville RA,Josephy PD,Kung RW,Wetmore SD

    更新日期：2020-02-17 00:00:00

  • Estrogen carcinogenesis: specific identification of estrogen-modified nucleobase in breast tissue from women.

    abstract：:Prolonged exposure to estrogens correlates with an increased risk for breast cancer. One explanation is that estrogen metabolites cause mutations by reacting with DNA, leading to depurination. We describe an extraction procedure and a liquid chromatographic tandem mass spectrometric (LC/MS/MS) assay to detect estrone-...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx8001737

    authors： Zhang Q,Aft RL,Gross ML

    更新日期：2008-08-01 00:00:00

  • The efficiencies of damage recognition and excision correlate with duplex destabilization induced by acetylaminofluorene adducts in human nucleotide excision repair.

    abstract：:Nucleotide excision repair (NER) removes lesions caused by environmental mutagens or UV light from DNA. A hallmark of NER is the extraordinarily wide substrate specificity, raising the question of how one set of proteins is able to recognize structurally diverse lesions. Two key features of good NER substrates are tha...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx3003033

    authors： Yeo JE,Khoo A,Fagbemi AF,Schärer OD

    更新日期：2012-11-19 00:00:00