Abstract:
:Paclitaxel, a potent antitumor agent, has been shown to be lipopolysaccharide (LPS) mimetic in mice, stimulating signaling pathways and gene expression indistinguishably from LPS. In the present study, we showed the intracellular signaling pathway of paclitaxel-induced nuclear factor-kappaB (NF-kappaB) activation and its suppressive effect on LPS-induced signaling in murine 70Z/3 pre-B cells. Stimulation of 70Z/3 cells with LPS for 30 min caused activation of NF-kappaB in the nuclei by detection of DNA-protein binding specific to NF-kappaB. Similarly, paclitaxel also produced a marked and dose-related NF-kappaB activation. However, pretreatment of cells with 10 microM paclitaxel for 18 h resulted in complete inhibition of LPS-mediated NF-kappaB activation. Interestingly, the activity of IkappaB kinase (IKK-beta), which plays an essential role in NF-kappaB activation through IkappaB phosphorylation, was largely enhanced in paclitaxel-treated cells, detected as IkappaBalpha phosphorylation. Because protein kinase C (PKC) is implicated in the activation of NF-kappaB via IKK-beta, the effect of paclitaxel on PKC activation was also measured. It was shown that NF-kappaB nuclear translocation and DNA binding in response to paclitaxel was completely blocked by the conventional PKC inhibitor, Gö 6976. Moreover, immunoblotting analysis with paclitaxel-treated cell extract demonstrated that the conventional PKC isotype PKC-alpha was found to be involved in the regulation of paclitaxel-induced NF-kappaB activation, as determined by electrophoretic mobility shift of PKC. Therefore, these data suggest that paclitaxel may activate IKK-beta via conventional PKC isotypes, resulting in NF-kappaB activation and, finally, desensitization of LPS-inducible signaling pathway in 70Z/3 pre-B cells.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Lee M,Jeon YJdoi
10.1124/mol.59.2.248keywords:
subject
Has Abstractpub_date
2001-02-01 00:00:00pages
248-53issue
2eissn
0026-895Xissn
1521-0111journal_volume
59pub_type
杂志文章abstract::The epipodophyllotoxin etoposide is an inhibitor of topoisomerase II. The effects of this agent on gene expression, particularly the transcriptional induction of genes implicated in growth control, are unknown. The present results demonstrate that etoposide induces expression of the c-jun protooncogene in HL-60 myeloi...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-06-01 00:00:00
abstract::Allosteric modulators of G-protein-coupled receptors can regulate conformational states involved in receptor activation ( Mol Pharmacol 58: 1412-1423, 2000 ). This hypothesis was investigated for the corticotropin-releasing factor type 1 (CRF(1)) receptor using a novel series of ligands with varying allosteric effect ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.042978
更新日期:2008-05-01 00:00:00
abstract::Beta-adrenergic receptors were characterized in a particulate fraction of human auricles obtained from patients operated upon for coronary insufficiency or valvular disease. [125I] Hydroxybenzylpindolol binding was evaluated in terms of kinetics; KD and Bmax values; and inhibition of binding in the presence of 10 micr...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1983-09-01 00:00:00
abstract::Our laboratory recently isolated and sequenced cDNAs encoding the microsomal flavin-containing monooxygenases (FMOs) from rabbit liver and rabbit lung. As a first step in understanding the molecular bases for the catalytic and physical differences between these enzymes, we have expressed them in COS-1 cells and compar...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00
abstract::The rat mu-opioid receptor clone in which novel exon 5 was found in the place of exon 4 (MOR-1B) was one of the first MOR-1 variants described. We now have identified the mouse homolog of the rat MOR-1B as well as four additional variants derived from splicing from exon 3 into different sites within exon 5. The sequen...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.105.011858
更新日期:2005-09-01 00:00:00
abstract::Healing of gastrointestinal mucosal lesions occurs through two processes: an early one involving cell migration and a later one in which cell division replaces lost cells. Both processes require the presence of polyamines, but the mechanism of action of these compounds is unknown. In the present study, we examined the...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-10-01 00:00:00
abstract::Quinones undergo redox cycling and/or arylation reactions with key biomolecules involved with cellular Ca2+ regulation. The present study utilizes nanomolar quantities of the fluorogenic maleimide 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin (CPM) to measure the reactivity of hyperreactive sulfhydryl moieti...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1999-05-01 00:00:00
abstract::The effect of endocytosis inhibitors on 5-hydroxytryptamine(2A) (5-HT(2A)) receptor desensitization and resensitization was examined in transiently transfected human embryonic kidney (HEK) 293 cells and in C6 glioma cells that endogenously express 5-HT(2A) receptors. In HEK-293 cells, 5-HT(2A) receptor desensitization...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.60.5.1020
更新日期:2001-11-01 00:00:00
abstract::Studies of the biochemical mechanisms evoked by conventional treatments for neoplastic diseases point to apoptosis as a key process for elimination of unwanted cells. Although the pathways through which chemotherapeutics promote cell death remain largely unknown, caspase proteases play a central role in the induction ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.53.3.446
更新日期:1998-03-01 00:00:00
abstract::The dopamine D3 receptor, although structurally similar to the dopamine D2 receptor, has 100-fold higher affinity for agonists such as dopamine and quinpirole, when these receptors are expressed in 293 cells. Additionally, the D3 receptor has generally lower affinity for several antagonists than does the D2 receptor. ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
abstract::Acetylsalicylic acid (aspirin) is a cyclooxygenase (COX) inhibitor, yet some of its therapeutic effects are thought to derive from mechanisms unrelated to prostaglandin synthesis inhibition. In human intestinal myofibroblasts, aspirin, at therapeutic doses, had the unexpected effect of inducing prolonged COX-2 express...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.65.2.470
更新日期:2004-02-01 00:00:00
abstract::The aptamer mechanism of action involves the direct interaction of oligonucleotide with protein and is responsible for the biological effects of many pharmacologically active oligodeoxynucleotides. In the work reported here, we have determined the effects of aptamers on the secondary, tertiary, and quaternary structur...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00
abstract::To determine the structural basis for binding subtype selective agonists in the beta-adrenergic receptor (beta AR), we examined the interaction of the mutant beta 2AR and chimeric beta 1/beta 2AR with a selective beta 2AR agonist, TA-2005 (8-hydroxy-5-[(1R)-1-hydroxy-2-[N-[(1R)-2-(p-methoxyphenyl)-1-methyle thy l] am...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.53.1.128
更新日期:1998-01-01 00:00:00
abstract::Neuronal cell degeneration was studied in vitro in primary rat brain neuronal cultures grown in serum-free, chemically defined, CDM R12 medium, by measuring lactate dehydrogenase (LDH) released in the culture medium. A Ca2+-dependent neuronal cell degeneration was observed after prolonged and transient exposure 30 mic...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-10-01 00:00:00
abstract::Bryostatin 1 and phorbol-12-myristate-13-acetate (PMA) are both potent activators of protein kinase C (PKC), although in primary mouse keratinocytes bryostatin 1 does not induce differentiation and blocks PMA-induced differentiation. We report here that in primary mouse keratinocytes PMA caused translocation of PKC-ep...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::The cannabinoid analog abnormal cannabidiol [abn-cbd; (-)-4-(3-3,4-trans-p-menthadien-[1,8]-yl)-olivetol] does not bind to CB(1) or CB(2) receptors, yet it acts as a full agonist in relaxing rat isolated mesenteric artery segments. Vasorelaxation by abn-cbd is endothelium-dependent, pertussis toxin-sensitive, and is i...
journal_title:Molecular pharmacology
pub_type: 评论,杂志文章
doi:10.1124/mol.63.3.699
更新日期:2003-03-01 00:00:00
abstract::Glioma cells with stem cell properties, termed glioma stem-like cells (GSCs), have been linked to tumor formation, maintenance, and progression and are responsible for the failure of chemotherapy and radiotherapy. Because conventional glioma treatments often fail to eliminate GSCs completely, residual surviving GSCs a...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.112.078402
更新日期:2012-09-01 00:00:00
abstract::Previous analyses suggested that potent aryl hydrocarbon receptor (AhR) antagonists were planar, with a lateral electron-rich center. To further define structural requirements and mechanism for antagonism, ten additional flavone derivatives were synthesized. Based on their ability to 1) compete with 2,3,7, 8-tetrachlo...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1999-04-01 00:00:00
abstract::Prostaglandin E(2) (PGE(2)), originally discovered as a pro-inflammatory mediator, also inhibits several chemoattractant-elicited neutrophil functions, including adhesion, secretion of cytotoxic enzymes, production of superoxide anions, and chemotaxis. In this study, we have examined the effects of PGE(2) and prostagl...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.66.2.293
更新日期:2004-08-01 00:00:00
abstract::Pertussis toxin (PTX) ADP-ribosylates alpha subunits of GTP-binding proteins (G proteins) when they are in association with beta gamma dimers, and free alpha subunits are thought not to be substrates under standard assay conditions. We now report the rather unexpected discovery that synthetic peptides encompassing the...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-11-01 00:00:00
abstract::Chick brain mRNA was isolated and injected into Xenopus oocytes. This led to the expression of gamma-aminobutyrate (GABA) channels easily accessible for current measurements using the voltage clamp technique. The effect of the anthelmintic natural product avermectin B1a on the GABA current was studied quantitatively. ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-12-01 00:00:00
abstract::The initial event upon binding of insulin-like growth factor 1 to the insulin-like growth factor type-I receptor (IGF-1R) is auto-phosphorylation of tyrosine residues within the activation loop of the kinase domain followed by phosphorylation of other receptor tyrosine residues and the subsequent activation of the int...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.040014
更新日期:2008-03-01 00:00:00
abstract::Our previous studies suggested that the dNTP/dNDP transporter systems that exist in mitochondria for transporting dNTP/dNDP from the cytoplasm to the mitochondria for mitochondrial DNA (mtDNA) synthesis play a critical role in delayed cytotoxicity of anti-human immunodeficiency virus (HIV) dideoxynucleoside analogs in...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.007120
更新日期:2005-02-01 00:00:00
abstract::Vasopressin receptor subtype(s) responsible for stimulation of insulin release from pancreatic beta cells were investigated by using subtype-selective antagonists and mice that were genetically lacking either V1a or V1b receptors. Arginine vasopressin (AVP) increased insulin release from isolated mouse islet cells in ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.65.3.623
更新日期:2004-03-01 00:00:00
abstract::Several structurally related series of folate analogs were studied as substrates for mouse liver folylpolyglutamate synthetase (FPGS). A comparison of the kinetics of the interaction of this enzyme with folate analogs that contained the quinazoline ring in place of the pteridine ring with those of the analogous pterid...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-11-01 00:00:00
abstract::AM1710 (3-(1,1-dimethyl-heptyl)-1-hydroxy-9-methoxy-benzo(c) chromen-6-one), a cannabilactone cannabinoid receptor 2 (CB2) agonist, suppresses chemotherapy-induced neuropathic pain in rodents without producing tolerance or unwanted side effects associated with CB1 receptors; however, the signaling profile of AM1710 re...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.118.113233
更新日期:2019-02-01 00:00:00
abstract::Several 2-amino-3-benzoylthiophenes were found to increase the binding of [3H]N6-cyclohexyladenosine to A1 adenosine receptors in rat brain membranes. Concentration-response curves were bell-shaped, with up to 45% stimulation of binding at 10 microM followed by inhibition at higher concentrations. Because these compou...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-12-01 00:00:00
abstract::Multidrug resistance protein 1 (MRP1) is a member of the "C" branch of the ATP-binding cassette transporter superfamily. The NH(2)-proximal nucleotide-binding domain (NBD1) of MRP1 differs functionally from its COOH-proximal domain (NBD2). NBD1 displays intrinsic high-affinity ATP binding and little ATPase activity. I...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.007708
更新日期:2005-06-01 00:00:00
abstract::We showed previously that microtubule disassembly by vinblastine induces the proto-oncogene c-myc in epithelial mammary HBL100 cells. In this study, we demonstrate that vinblastine treatment in these cells, in contrast to what was observed with the colon adenocarcinoma cell line HT29-D4, activated the transcription fa...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.59.5.1165
更新日期:2001-05-01 00:00:00
abstract::Neuroactive steroids have been postulated to cause anesthesia by binding to unique steroid recognition sites on gamma-aminobutyric acid (GABA) receptors and modulating GABA receptor function. Steroids interact with these sites diastereoselectively, but it is unknown whether steroid sites show enantioselectivity. To ad...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-12-01 00:00:00