Abstract:
:To determine the role of C-Rel in nitric-oxide synthase-2 (NOS-2) transcriptional activation, we evaluated the effect of lipopolysaccharide and interferon-gamma (LPS/IFNgamma) on C-Rel DNA binding in RAW 264.7. LPS/IFNgamma-stimulated C-Rel binding peaked at 4 to 8 h and declined at 24 h. Transfection of cells with a C-Rel small interfering RNA abrogated C-Rel binding at all time points. LPS/IFNgamma produced superoxide at 4 h, which subsided at 8 h. C-Rel binding and NOS-2 expression were abrogated by superoxide dismutase or apocynin at 4 h, suggesting a key role that superoxide plays in mediating C-Rel binding and NOS-2 transactivation only at 4 h. We have reported previously that salicylate at 10(-5) M inhibited LPS/IFNgamma-induced CCAAT/enhancer binding protein beta (C/EBPbeta) binding at 4 h but not at 8 or 24 h. A single dose of salicylate did not inhibit C-Rel binding at any time point. The addition of a second dose of salicylate 4 h before an indicated endpoint suppressed C-Rel but not C/EBPbeta or interferon-gamma-regulated factor-1 binding at 8 and 24 h. A single dose of salicylate added with LPS/IFNgamma inhibited NOS-2 expression only at 4 h. However, salicylate supplement inhibited NOS-2 promoter activities and mRNA and protein levels throughout 24 h. Signal profiling with a panel of inhibitors revealed time-dependent switch of signaling pathways. These results demonstrate temporal regulation of transactivator binding by LPS/IFNgamma via evolving signaling pathways. We propose that salicylate inhibits C/EBPbeta binding at 4 h and C-Rel binding at 8 and 24 h by targeting related kinases.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Cieslik KA,Deng WG,Wu KKdoi
10.1124/mol.106.026054subject
Has Abstractpub_date
2006-12-01 00:00:00pages
2004-14issue
6eissn
0026-895Xissn
1521-0111pii
mol.106.026054journal_volume
70pub_type
杂志文章abstract::Platelet-derived growth factor (PDGF) and PDGF receptors (PDGFRs) are ubiquitously expressed in the mammalian central nervous system, where they exert trophic actions on both neuronal and glial cells. However, the acute actions of PDGF on synaptic transmission are unknown. We report a novel regulatory action of PDGF/P...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract::By limiting unrestricted activation of intracellular effectors, compartmentalised signalling of cyclic nucleotides confers specificity to extracellular stimuli and is critical for the development and health of cells and organisms. Dissecting the molecular mechanisms that allow local control of cyclic nucleotide signal...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.119.118869
更新日期:2020-02-28 00:00:00
abstract::The level of cellular ceramide, an apoptotic rheostat, is increased by sphingomyelinase or de novo synthesis. The expression of the glutathione S-transferase (GST) gene, whose induction accounts for cell viability, is regulated by activation of CCAAT/enhancer binding protein-beta (C/EBPbeta) and NF-E2-related factor-2...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.65.6.1475
更新日期:2004-06-01 00:00:00
abstract::Rates of glucuronidation were measured at high substrate concentrations in specific zones of the liver lobule using micro-light guides placed on periportal and pericentral regions on the surface of livers from phenobarbital-treated rats. Livers were perfused with sulfate-free buffer under normoxic conditions, and fluo...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1984-05-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) are synthesized in response to diverse stimuli, including cytokines, growth factors, hormones, and oxidative stress. Here we show that the nitric oxide (NO) donor 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA-NO) and NO from murine macrophages transcriptionally regulate MMP-13 expressi...
journal_title:Molecular pharmacology
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更新日期:2002-10-01 00:00:00
abstract::The therapeutic potential of antitumor drugs is seriously limited by the manifestation of cellular drug resistance. We used the budding yeast Saccharomyces cerevisiae as a model system to identify novel mechanisms of resistance to one of the most active anticancer agents, cisplatin. We pinpointed NPR2 (nitrogen permea...
journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:2003-08-01 00:00:00
abstract::The isoprenoid donor for protein geranylgeranylation reactions, geranylgeranyl diphosphate (GGDP), is the product of the enzyme GGDP synthase (GGDPS) that condenses farnesyl diphosphate (FDP) and isopentenyl pyrophosphate. GGDPS inhibition is of interest from a therapeutic perspective for multiple myeloma because we h...
journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:2017-03-01 00:00:00
abstract::The effect of the thiol-alkylating agent, N-ethylmaleimide (NEM), on histamine (HA) H1-receptors from guinea pig cerebellum, labeled with [3H]mepyramine, was investigated. The properties of [3H]mepyramine binding (apparent dissociation constant and maximal number of sites) were not modified by prior treatment of the m...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1985-08-01 00:00:00
abstract::High expression of the aflatoxin B1 (AFB1)-8,9-epoxide-conjugating glutathione S-transferase A3 (mGSTA3) subunit in mouse liver confers intrinsic resistance to AFB1 hepatocarcinogenesis. It is not known how the gene encoding this protein is regulated. The murine mGSTA3 gene has been identified using bioinformatics. It...
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pub_type: 杂志文章
doi:10.1124/mol.64.5.1018
更新日期:2003-11-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-06-01 00:00:00
abstract::Westernization of dietary habits increases lipid intake and is responsible for increased numbers of patients with atherosclerotic diseases. Niemann-Pick C1-Like 1 (NPC1L1)-a cholesterol importer-plays a crucial role in dietary cholesterol absorption in the intestine and is closely associated with several lipid-related...
journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:2019-07-01 00:00:00
abstract::G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) act in concert to regulate cell growth, proliferation, survival, and migration. Metabotropic GABAB receptor (GABABR) is the GPCR for the main inhibitory neurotransmitter GABA in the central nervous system. Increased expression of GABABR has been ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.107854
更新日期:2017-09-01 00:00:00
abstract::Multidrug resistance-associated protein 2 (MRP2) transports glutathione conjugates, glucuronide conjugates, and sulfated conjugates of bile acids. In the present study, we examined the role of charged amino acids in the transmembrane domains of rat Mrp2, conserved among MRP families, using the isolated membrane vesicl...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.59.5.1077
更新日期:2001-05-01 00:00:00
abstract::We compared the binding of [N-methyl-3H]scopolamine methyl chloride [( 3H]NMS) and pirenzepine to muscarinic receptors in four regions of the rat central nervous system (cortex, hippocampus, striatum, and cerebellum) and in rat heart. Equilibrium binding studies suggested the existence of three classes of receptors: A...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-10-01 00:00:00
abstract::TWIK-related K+ channel TREK1, a background leak K+ channel, has been strongly implicated as the target of several general and local anesthetics. Here, using the whole-cell and single-channel patch-clamp technique, we investigated the effect of lidocaine, a local anesthetic, on the human (h)TREK1 channel heterologousl...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.056838
更新日期:2009-10-01 00:00:00
abstract::Depolarization-induced 86Rb efflux, an index of K+ efflux, was developed by using mammalian cultured spinal cord neurons to study the effect of gamma aminobutyric acid (GABAB) receptor activation on Ca2(+)-activated K(+)-channels. The Ca2(+)-activated 86Rb efflux was obtained by using two methods. The first method uti...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-09-01 00:00:00
abstract::Signaling by G-protein-coupled receptors is often considered a uniform process, whereby a homogeneously activated proportion of randomly distributed receptors are activated under equilibrium conditions and produce homogeneous, steady-state intracellular signals. While this may be the case in some biologic systems, the...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
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更新日期:2015-09-01 00:00:00
abstract::Previous studies have shown that at least two subtypes of somatostatin (SRIF) receptors (SRIF1 and SRIF2) are expressed in mammalian cells. SRIF1 receptors have high affinity for MK 678, whereas SRIF2 receptors have no affinity for MK 678 but selectively bind peptides with structures similar to that of CGP 23996. Rece...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-07-01 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::Tumor suppressor gene BRCA1 is frequently mutated in familial breast and ovarian cancer. BRCA1 plays pivotal roles in maintaining genomic stability by interacting with numerous proteins in cell cycle control and DNA repair. Irofulven (6-hydroxymethylacylfulvene, HMAF, MGI 114, NSC 683863) is one of a new class of anti...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.106.029504
更新日期:2007-04-01 00:00:00
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
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更新日期:2003-08-01 00:00:00
abstract::Bufuralol 1'-hydroxylation is a prototypical reaction catalyzed by cytochrome P450 (P450) 2D6, an enzyme known to show debrisoquine/sparteine-type genetic polymorphism in humans. In the present study we further examined the roles of several human P450 enzymes, as well as P450 2D6, in the hydroxylation of (+/-)-bufural...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::Melanocortins (MCs) have various physiological actions on the brain. The recent cloning of neural MC receptors opened new avenues to study the effects of these neuropeptides on the nervous system. Here we investigated the structure-activity relationships (SARs) of peptides derived from adrenocorticotropic hormone (ACT...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::The co-transfection assay is a novel functional assay using cells transiently transfected with plasmids encoding intracellular receptors and corresponding reporter genes. Using this assay, natural product extracts were tested to identify compounds that modulate intracellular receptor activity, measured as changes in r...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::We identified a novel azaindole derivative, L-750,667, that has high affinity (Ki = 0.51 nM) and >2000-fold selectivity for D4 dopamine receptors compared with its activity at D2 and D3 dopamine receptors. L-750,667 had little affinity for rat D1/D5 dopamine receptors, sigma binding sites, or 5-hydroxytryptamine1A or ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-12-01 00:00:00
abstract::We have identified four new mu-opiod receptor (MOR)-1 exons, indicating that the gene now contains at least nine exons spanning more than 200 kilobases. Replacement of exon 4 by combinations of the new exons yields three new receptors. When expressed in Chinese hamster ovary cells, all three variants displayed high af...
journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:1999-08-01 00:00:00
abstract::Increasing data indicate that brain endocannabinoid system plays a role in the effects of antidepressant medications. Here we examined the effect of in vivo exposure to the selective serotonin uptake inhibitor fluoxetine on cannabinoid type 1 (CB(1)) receptor density and functionality in the rat prefrontal cortex (PFC...
journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:2010-03-01 00:00:00
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journal_title:Molecular pharmacology
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doi:10.1124/mol.108.052209
更新日期:2009-05-01 00:00:00
abstract::Upon sustained insult, kinins are released and many kinin responses, such as inflammatory pain, adapt from a B2 receptor (B2R) type in the acute phase to a B1 receptor (B1R) type in the chronic phase. In this study, we show that kinins modulate receptor endocytosis to rapidly decrease B2R and increase B1R on the cell ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:2007-02-01 00:00:00
abstract::We compared the efficiencies with which human alpha 1-adrenergic receptor (AR) subtypes activate inositol phosphate (InsP) formation and increase intracellular Ca2+ in transfected cell lines. Expression of human alpha 1a-, alpha 1b-, and alpha 1d-AR cDNAs under the repressible control of anhydrotetracycline in human e...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-11-01 00:00:00