当前位置： SCI文献检索 > MOLECULAR PHARMACOLOGY期刊下所有文献 > Oxidative Stress and Response to Thymidylate Synthase-Targeted Antimetabolites.

Oxidative Stress and Response to Thymidylate Synthase-Targeted Antimetabolites.

Abstract：

:Thymidylate synthase (TYMS; EC 2.1.1.15) catalyzes the reductive methylation of 2'-deoxyuridine-5'-monophosphate (dUMP) by N(5),N(10)-methyhlenetetrahydrofolate, forming dTMP for the maintenance of DNA replication and repair. Inhibitors of TYMS have been widely used in the treatment of neoplastic disease. A number of fluoropyrimidine and folate analogs have been developed that lead to inhibition of the enzyme, resulting in dTMP deficiency and cell death. In the current study, we have examined the role of oxidative stress in response to TYMS inhibitors. We observed that intracellular reactive oxygen species (ROS) concentrations are induced by these inhibitors and promote apoptosis. Activation of the enzyme NADPH oxidase (NOX), which catalyzes one-electron reduction of O2 to generate superoxide (O2 (●-)), is a significant source of increased ROS levels in drug-treated cells. However, gene expression profiling revealed a number of other redox-related genes that may contribute to ROS generation. TYMS inhibitors also induce a protective response, including activation of the transcription factor nuclear factor E2-related factor 2 (NRF2), a critical mediator of defense against oxidative and electrophilic stress. Our results show that exposure to TYMS inhibitors induces oxidative stress that leads to cell death, while simultaneously generating a protective response that may underlie resistance against such death.

journal_name

Mol Pharmacol

journal_title

Molecular pharmacology

authors

Ozer U,Barbour KW,Clinton SA,Berger FG

doi

10.1124/mol.115.099614

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

970-81

issue

6

eissn

0026-895X

issn

1521-0111

pii

mol.115.099614

journal_volume

88

pub_type

杂志文章

相关文献

MOLECULAR PHARMACOLOGY文献大全
  • Photoaffinity labeling of the partially purified mitochondrial phenylalkylamine calcium antagonist receptor.

    abstract：:Mitochondria contain specific Ca2+ antagonist binding sites that are associated with an inner mitochondrial membrane anion channel. These mitochondrial Ca2+ antagonist receptors can be solubilized with digitonin and partially purified [as assessed by postreversible (+/-)-[3H]nitrendipine binding] using ion exchange ch...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Zernig G

    更新日期：1992-12-01 00:00:00

  • Expression of A3 adenosine receptors in human lymphocytes: up-regulation in T cell activation.

    abstract：:The present study investigates mRNA and protein levels of A3 adenosine receptors in resting (R) and activated (A) human lymphocytes. The receptors were evaluated by the antagonist radioligand [3H]5-N-(4-methoxyphenyl-carbamoyl)amino-8-propyl-2(2furyl)-pyrazolo-[4,3e]-1,2,4-triazolo-[1,5-c]-pyrimidine ([3H]MRE 3008F20)...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.65.3.711

    authors： Gessi S,Varani K,Merighi S,Cattabriga E,Avitabile A,Gavioli R,Fortini C,Leung E,Mac Lennan S,Borea PA

    更新日期：2004-03-01 00:00:00

  • Voltage-dependent inhibition of N- and P-type calcium channels by the peptide toxin omega-grammotoxin-SIA.

    abstract：:We studied the mechanism by which the peptide omega-grammotoxin-SIA inhibits voltage-dependent calcium channels. Grammotoxin at concentrations of > 50 nM completely inhibited inward current carried by 2 mM barium through P-type channels in rat cerebellar Purkinje neurons when current was elicited by depolarizations up...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.52.6.1095

    authors： McDonough SI,Lampe RA,Keith RA,Bean BP

    更新日期：1997-12-01 00:00:00

  • Ethanol reduces GABAA alpha1 subunit receptor surface expression by a protein kinase Cgamma-dependent mechanism in cultured cerebral cortical neurons.

    abstract：:Prolonged ethanol exposure causes central nervous system hyperexcitability that involves a loss of GABAergic inhibition. We previously demonstrated that long-term ethanol exposure enhances the internalization of synaptic GABA(A) receptors composed of alpha1beta2/3gamma2 subunits. However, the mechanisms of ethanol-med...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.109.063016

    authors： Kumar S,Suryanarayanan A,Boyd KN,Comerford CE,Lai MA,Ren Q,Morrow AL

    更新日期：2010-05-01 00:00:00

  • Phosphatidylinositol-4,5-bisphosphate: actin dynamics and the regulation of ATP-dependent and -independent secretion.

    abstract：:It has long been believed that the cortical actin cytoskeleton plays an important role in regulating the secretion of hormones and neurotransmitters. In this study, we investigated the control of actin dynamics in primary neuroendocrine cells and determined the relationship of actin dynamics to various components of t...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.104.008474

    authors： Bittner MA,Holz RW

    更新日期：2005-04-01 00:00:00

  • State-dependent etomidate occupancy of its allosteric agonist sites measured in a cysteine-substituted GABAA receptor.

    abstract：:A central axiom of ligand-receptor theory is that agonists bind more tightly to active than to inactive receptors. However, measuring agonist affinity in inactive receptors is confounded by concomitant activation. We identified a cysteine substituted mutant γ-aminobutyric acid type A (GABAA) receptor with unique chara...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.112.084558

    authors： Stewart DS,Hotta M,Desai R,Forman SA

    更新日期：2013-06-01 00:00:00

  • Cysteine Scanning Mutagenesis of TM4b-4c Loop of Glutamate Transporter EAAT1 Reveals Three Conformationally Sensitive Residues.

    abstract：:Glutamatergic synaptic transmitters are cleared from the synaptic cleft through excitatory amino acid transporters (EAATs) that are responsible for recycling glutamate and transporting it into neurons and glial cells. To probe the structural role of the TM4b-4c loop of EAAT1 (Rattus norvegicus), each of the 57 amino a...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.117.111245

    authors： Zhang W,Zhang X,Qu S

    更新日期：2018-07-01 00:00:00

  • Identification and characterization of compounds that potentiate NT-3-mediated Trk receptor activity.

    abstract：:Neurotrophins are a family of secreted proteins that play an important role in the development, differentiation, and survival of neurons. Studies also suggest that aberrant neurotrophin signaling may play a role in processes underlying disease states such as schizophrenia, Alzheimer's disease, and depression. Whereas ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.105.020255

    authors： Lewis MA,Hunihan L,Franco D,Robertson B,Palmer J,Laurent DR,Balasubramanian BN,Li Y,Westphal RS

    更新日期：2006-04-01 00:00:00

  • Metabolism and mode of inhibition of varicella-zoster virus by L-beta-5-bromovinyl-(2-hydroxymethyl)-(1,3-dioxolanyl)uracil is dependent on viral thymidine kinase.

    abstract：:A nonnaturally occurring L-configuration nucleoside analog, L-beta-5-bromovinyl-(2-hydroxymethyl)-1,3-(dioxolanyl)uracil (L-BVOddU) selectively inhibited varicella-zoster virus growth in human embryonic lung (HEL) 299 cell culture with an EC(50) of 0.055 microM, whereas no inhibition of CEM and HEL 299 cell growth or ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.58.5.1109

    authors： Li L,Dutschman GE,Gullen EA,Tsujii E,Grill SP,Choi Y,Chu CK,Cheng YC

    更新日期：2000-11-01 00:00:00

  • Down-regulation of STAT5b transcriptional activity by ligand-activated peroxisome proliferator-activated receptor (PPAR) alpha and PPARgamma.

    abstract：:The nuclear receptor peroxisome proliferator-activated receptor (PPAR) is activated by a diverse group of acidic ligands, including many peroxisome proliferator chemicals present in the environment. Janus tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) signaling is activated by multiple cyt...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.64.2.355

    authors： Shipley JM,Waxman DJ

    更新日期：2003-08-01 00:00:00

  • Modeling the effects of β1-adrenergic receptor blockers and polymorphisms on cardiac myocyte Ca2+ handling.

    abstract：:β-Adrenergic receptor blockers (β-blockers) are commonly used to treat heart failure, but the biologic mechanisms governing their efficacy are still poorly understood. The complexity of β-adrenergic signaling coupled with the influence of receptor polymorphisms makes it difficult to intuit the effect of β-blockers on ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.113.090951

    authors： Amanfu RK,Saucerman JJ

    更新日期：2014-08-01 00:00:00

  • S-nitrosylating agents: a novel class of compounds that increase cystic fibrosis transmembrane conductance regulator expression and maturation in epithelial cells.

    abstract：:The endogenous bronchodilator, S-nitrosoglutathione (GSNO), increases expression, maturation, and function of both the wild-type and the DeltaF508 mutant of the cystic fibrosis transmembrane conductance regulatory protein (CFTR). Though transcriptional mechanisms of action have been identified, GSNO seems also to have...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.106.023242

    authors： Zaman K,Carraro S,Doherty J,Henderson EM,Lendermon E,Liu L,Verghese G,Zigler M,Ross M,Park E,Palmer LA,Doctor A,Stamler JS,Gaston B

    更新日期：2006-10-01 00:00:00

  • Prostaglandin E receptor EP1 forms a complex with dopamine D1 receptor and directs D1-induced cAMP production to adenylyl cyclase 7 through mobilizing G(βγ) subunits in human embryonic kidney 293T cells.

    abstract：:The mechanism underlying the crosstalk between multiple G protein-coupled receptors remains poorly understood. We previously reported that prostaglandin E receptor EP1 facilitates dopamine D1 receptor signaling in striatal slices and promotes behavioral responses induced by D1 receptor agonists. Here, using human embr...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.113.087288

    authors： Ehrlich AT,Furuyashiki T,Kitaoka S,Kakizuka A,Narumiya S

    更新日期：2013-09-01 00:00:00

  • Tricyclic antidepressants and dextromethorphan bind with higher affinity to the phencyclidine receptor in the absence of magnesium and L-glutamate.

    abstract：:Recent studies from our laboratory have provided evidence that multiple states of the phencyclidine (PCP) receptor exist. In addition, several compounds such as PCP and the novel anticonvulsant MK-801 were found to inhibit binding more potently in the presence of Mg2+ and L-glutamate (L-GLU) than when these agents wer...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Sills MA,Loo PS

    更新日期：1989-07-01 00:00:00

  • Human gene S31 encodes the pharmacologically defined serotonin 5-hydroxytryptamine1E receptor.

    abstract：:The gene encoding a human 5-hydroxytryptamine (5-HT)1 receptor subtype was isolated from a human placental genomic library by using oligonucleotide probes derived from transmembrane regions of the cloned human 5-HT1D beta receptor. The deduced amino acid sequence of the genomic clone hp75d is identical to that of the ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Zgombick JM,Schechter LE,Macchi M,Hartig PR,Branchek TA,Weinshank RL

    更新日期：1992-08-01 00:00:00

  • Long term beta-adrenoceptor-mediated up-regulation of Gi alpha and G(o) alpha mRNA levels and pertussis toxin-sensitive guanine nucleotide-binding proteins in rat heart.

    abstract：:Chronic stimulation of beta-adrenoceptors leads to increased mRNA and protein levels of pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G proteins) in the heart. In the present study the time course is reported of the effect of isoprenaline infusions on myocardial mRNA levels of Gi alpha-2, Gi alp...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Eschenhagen T,Mende U,Diederich M,Nose M,Schmitz W,Scholz H,Schulte am Esch J,Warnholtz A,Schäfer H

    更新日期：1992-11-01 00:00:00

  • Caveolins as Regulators of Stress Adaptation.

    abstract：:Caveolins have been recognized over the past few decades as key regulators of cell physiology. They are ubiquitously expressed and regulate a number of processes that ultimately impact efficiency of cellular processes. Though not critical to life, they are central to stress adaptation in a number of organs. The follow...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章,评审

    doi：10.1124/mol.117.111237

    authors： Schilling JM,Head BP,Patel HH

    更新日期：2018-04-01 00:00:00

  • Characterization of specific binding sites for [3H](d)-N-allylnormetazocine in rat brain membranes.

    abstract：:Binding of [3H](d)-N-allylnormetazocine ([3H](d)-NANM) to rat brain membranes is stereospecific, reversible, and saturable (Bmax = 260 fmol/mg of protein) and manifests moderately high affinity (Kd = 20 nM). The rank order of potency among opioidbenzomorphans and phencyclidine (PCP) analogs for competition for [3H](d)...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Itzhak Y,Hiller JM,Simon EJ

    更新日期：1985-01-01 00:00:00

  • Early life stress causes refractoriness to haloperidol-induced catalepsy.

    abstract：:The use of classic antipsychotic drugs is limited by the occurrence of extrapyramidal motor symptoms, which are caused by dopamine (DA) receptor blockade in the neostriatum. We examined the impact of early-life stress on haloperidol-induced catalepsy using the rat model of prenatal restraint stress (PRS). Adult "PRS r...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.113.085530

    authors： Marrocco J,Mairesse J,Bucci D,Lionetto L,Battaglia G,Consolazione M,Ravasi L,Simmaco M,Morley-Fletcher S,Maccari S,Nicoletti F

    更新日期：2013-08-01 00:00:00

  • Fusion polypeptides that inhibit exocytosis: fusing aptamer and cell-penetrating peptide technologies and pharmacologies.

    abstract：:Cell-penetrating peptides are amphipathic or cationic oligopeptides able to transport covalently attached cargoes across cell membranes. Peptide aptamers are polypeptide fragments of endogenous proteins that mimic and thus perturb interactions with other cellular proteins. Combining aptamer and CPP technology can gene...

    journal_title：Molecular pharmacology

    pub_type： 评论,杂志文章

    doi：10.1124/mol.105.011429

    authors： Eiden LE

    更新日期：2005-04-01 00:00:00

  • Interactions between the Mas-related receptors MrgD and MrgE alter signalling and trafficking of MrgD.

    abstract：:When expressed via an inducible promoter in human embryonic kidney 293 cells, the rat Mas-related gene D (rMrgD) receptor responded to beta-alanine but not L-alanine by elevating intracellular [Ca(2+)], stimulating phosphorylation of the mitogenactivated protein kinases known as extracellular signal-regulated kinase (...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.105.018788

    authors： Milasta S,Pediani J,Appelbe S,Trim S,Wyatt M,Cox P,Fidock M,Milligan G

    更新日期：2006-02-01 00:00:00

  • Antitumor mechanisms of systemically administered epidermal growth factor receptor antisense oligonucleotides in combination with docetaxel in squamous cell carcinoma of the head and neck.

    abstract：:Squamous cell carcinoma of the head and neck (SCCHN) is one of the most common malignancies worldwide, with low 5-year survival rates. Current strategies that block epidermal growth factor receptor (EGFR) have limited effects when administered as single agents. Targeting EGFR via intratumoral administration of phospho...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.107.041160

    authors： Thomas SM,Ogagan MJ,Freilino ML,Strychor S,Walsh DR,Gooding WE,Grandis JR,Zamboni WC

    更新日期：2008-03-01 00:00:00

  • Endocannabinoid 2-arachidonyl glycerol is a full agonist through human type 2 cannabinoid receptor: antagonism by anandamide.

    abstract：:The endocannabinoids anandamide and 2-arachidonyl glycerol (2-AG) bind to G protein-coupled central and peripheral cannabinoid receptors CB1 and CB2, respectively. Due to the relatively high expression of the CB2 isotype on peripheral immune cells, it has been hypothesized that this receptor mediates the immunosuppres...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Gonsiorek W,Lunn C,Fan X,Narula S,Lundell D,Hipkin RW

    更新日期：2000-05-01 00:00:00

  • Probing interactions between viral DNA and human immunodeficiency virus type 1 integrase using dinucleotides.

    abstract：:Retroviral integrases are essential for viral replication and represent an attractive chemotherapeutic target. In the current study, we demonstrated the activity of micromolar concentrations of dinucleotides against human immunodeficiency virus type 1 (HIV-1), HIV type 2 (HIV-2), simian immunodeficiency virus, and fel...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.51.4.567

    authors： Mazumder A,Uchida H,Neamati N,Sunder S,Jaworska-Maslanka M,Wickstrom E,Zeng F,Jones RA,Mandes RF,Chenault HK,Pommier Y

    更新日期：1997-04-01 00:00:00

  • Peroxisome proliferator-activated receptor gamma-independent repression of prostate-specific antigen expression by thiazolidinediones in prostate cancer cells.

    abstract：:In light of the potential use of the thiazolidinedione family of peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists in prostate cancer treatment, this study assessed the mechanism by which these agents suppress prostate-specific antigen (PSA) secretion in prostate cancer cells. Two lines of evidence...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.105.018333

    authors： Yang CC,Ku CY,Wei S,Shiau CW,Chen CS,Pinzone JJ,Ringel MD,Chen CS

    更新日期：2006-05-01 00:00:00

  • Functional mapping of the transient receptor potential vanilloid 1 intracellular binding site.

    abstract：:Capsaicin (vanilloid) sensitivity has long served as the functional signature of a subset of nociceptive sensory neurons. Mutagenesis studies have revealed seemingly distinct regions involved in mediating ligand binding and channel activation at the capsaicin binding site. Residue 547 (transmembrane region 4) mediates...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.106.023945

    authors： Johnson DM,Garrett EM,Rutter R,Bonnert TP,Gao YD,Middleton RE,Sutton KG

    更新日期：2006-09-01 00:00:00

  • Differential modification of striatal D1 dopamine receptors and effector moieties by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in vivo and in vitro.

    abstract：:Both in vivo and in vitro treatments with the irreversible protein-modifying reagent, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), were used to investigate rat striatal D1 dopamine receptor/effector interactions. Peripherally administered EEDQ markedly reduced D1 dopamine receptor binding and D1 dopamine rec...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Hess EJ,Battaglia G,Norman AB,Creese I

    更新日期：1987-01-01 00:00:00

  • Modulation of platelet-derived growth factor B mRNA abundance in macrophages by colchicine and dibutyryl-cAMP.

    abstract：:Macrophage production of growth factors for fibroblasts, in particular platelet-derived growth factor B [PDGF(B)] and transforming growth factor-beta (TGF-beta), is thought to be central to the pathogenesis of pulmonary fibrosis. In a search for anti-inflammatory agents that might prevent this process, we asked whethe...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Wangoo A,Haynes AR,Sutcliffe SP,Sorooshian M,Shaw RJ

    更新日期：1992-10-01 00:00:00

  • Delta 9-tetrahydrocannabinol inhibits arachidonic acid acylation of phospholipids and triacylglycerols in guinea pig cerebral cortex slices.

    abstract：:We reported earlier that delta 9-tetrahydrocannabinol (THC), the main psychoactive ingredient in marihuana, increased markedly the level of unesterified arachidonic acid (AA) in guinea pig cerebral cortex slices prelabeled with [14C]AA. The purpose of the present study was to clarify the mechanism underlying THC-enhan...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Reichman M,Nen W,Hokin LE

    更新日期：1991-10-01 00:00:00

  • Nuclear factor-kappa B contributes to excitotoxin-induced apoptosis in rat striatum.

    abstract：:Excitotoxin-induced destruction of striatal neurons, proposed as a model of Huntington's disease, involves a process having the biochemical stigmata of apoptosis. Recent studies suggested that transcription factor nuclear factor (NF)-kappa B may be involved in excitotoxicity. To further analyze the contribution of NF ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.53.1.33

    authors： Qin ZH,Wang Y,Nakai M,Chase TN

    更新日期：1998-01-01 00:00:00