Effect of staurosporine on transcription factor NF-kappaB in human keratinocytes.


:Activation of the transcription factor NF-kappaB is known to be important in the regulated expression of a large number of pro-inflammatory genes including interleukin-8 (IL-8). Previously, we showed that the protein kinase inhibitor staurosporine potentiates IL-1-stimulated IL-8 production in human keratinocytes. Moreover, recent studies by other investigators demonstrated that staurosporine treatment alone results in a concentration-dependent increase in IL-8 mRNA and protein production. Therefore, in order to understand the mechanism underlying this observation, the effect of staurosporine on the activation of NF-kappaB was investigated. Electrophoretic mobility shift assays using an oligonucleotide containing the NF-kappaB consensus motif demonstrated that staurosporine treatment resulted in the activation of NF-kappaB by 15 min post-treatment. The ability of staurosporine to activate NF-kappaB was investigated further, using luciferase reporters under the control of the HIV-LTR or IL-8 core promoter transfected into human U937 cells. Stimulation with staurosporine resulted in a concentration-dependent induction of luciferase activity. In contrast, the very selective protein kinase C inhibitor 3-[8-[(dimethylamino)methyl]-6,7,8,9-tetrahydropyrido-[1,2-a]indol -10-yl]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione hydrochloride (Ro32-0432) did not stimulate the activation of NF-kappaB, as measured in the luciferase reporter assay. The mechanism underlying NF-kappaB activation does not appear to involve the classical activation pathways in that staurosporine does not induce the disappearance of IkappaB family members. In conclusion, staurosporine appears to stimulate the activation of NF-kappaB in at least two cell types, and this effect appears to be independent of protein kinase C.


Biochem Pharmacol


Biochemical pharmacology


Chabot-Fletcher M,Breton JJ




Has Abstract


1998-07-01 00:00:00














  • Structural changes of rat liver microsomal membranes induced by the oral administration of carbon tetrachloride. 31P-NMR and spin-label studies.

    abstract::The acute effects of carbon tetrachloride (CCl4) on the membrane structure of rat liver microsomes were studied using 31P-NMR and spin-labeling techniques. 31P-NMR spectra of rat liver microsomes were not changed appreciably after the oral administration of CCl4, indicating that the surface structures of microsomal me...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Utsumi H,Murayama J,Hamada A

    更新日期:1985-01-01 00:00:00

  • Prevention of binding of rgp120 by anti-HIV active tannins.

    abstract::Several tannins with anti-HIV activity have been described previously (Nonaka et al., J Nat Prod 53: 587-595, 1990). We have shown that the tannins chebulinic acid and punicalin were able to block the binding of HIV rgp120 to CD4. These compounds were not toxic to stimulated human peripheral blood lymphocytes at conce...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Weaver JL,Pine PS,Dutschman G,Cheng YC,Lee KH,Aszalos A

    更新日期:1992-06-09 00:00:00

  • Inhibition of glutathione reductase by flavonoids. A structure-activity study.

    abstract::A structure-activity study of fourteen chemically related flavonoids was conducted to evaluate their abilities to inhibit glutathione reductase (GR). By comparing the I50 values of flavonoids from different classes possessing an identical hydroxyl configuration, we determined the following order of potency for inhibit...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Elliott AJ,Scheiber SA,Thomas C,Pardini RS

    更新日期:1992-10-20 00:00:00

  • Role of the CYP2D subfamily in metabolism-dependent covalent binding of propranolol to liver microsomal protein in rats.

    abstract::In vitro covalent binding of a chemically reactive metabolite of propranolol to microsomal macromolecules, which is presumed to cause inhibition of its own metabolism in rats, was diminished in liver microsomes from rats pretreated with propranolol. Covalent binding was suppressed by the addition of an antibody agains...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Masubuchi Y,Narimatsu S,Hosokawa S,Suzuki T

    更新日期:1994-11-16 00:00:00

  • Binding of [3H]perhydrohistrionicotoxin and [3H]phencyclidine to the nicotinic receptor-ion channel complex of Torpedo electroplax. Inhibition by histrionicotoxins and derivatives.

    abstract::Histrionicotoxin, a spiropiperidine alkaloid, and twenty-two analogs inhibited binding of [3H]perhydrohistrionicotoxin [( 3H]H12-HTX) and of [3H]phencyclidine [( 3H]PCP) to sites on the acetylcholine receptor-ion complex of Torpedo electroplax membranes. Structural alterations to the nitrogen (secondary amine) or oxyg...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Aronstam RS,King CT Jr,Albuquerque EX,Daly JW,Feigl DM

    更新日期:1985-09-01 00:00:00

  • A checkerboard method to evaluate interactions between drugs.

    abstract::A method to evaluate interactions between biologically active agents is presented. Synergism, zero interaction, and antagonism were easily detected with the three-dimensional approach proposed herein. This method is compatible with a checkerboard design to diagnose the interaction between agents and obviate the need t...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Martinez-Irujo JJ,Villahermosa ML,Alberdi E,Santiago E

    更新日期:1996-03-08 00:00:00

  • Characterization of specific [3H]dimethylstaurosporine binding to protein kinase C.

    abstract::The microbial alkaloid staurosporine is a member of a recently described family of protein kinase inhibitors. [N,N-dimethyl-3H]N-dimethylstaurosporine ([3H]DMS) was prepared from staurosporine by methylation with [3H]methyl iodide. Since staurosporine inhibits protein kinase C (PKC) most potently, the binding of [3H]D...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Gross JL,Herblin WF,Do UH,Pounds JS,Buenaga LJ,Stephens LE

    更新日期:1990-07-15 00:00:00

  • An indirubin derivative, E804, exhibits potent angiosuppressive activity.

    abstract::Angiogenesis, the development of neovessels from pre-existing vessels, is obligatory for solid tumors survival, growth, invasion, and metastasis. Many anti-angiogenic agents are small molecules originated from natural sources. Recently, angiosuppressive effects of indirubin and its derivatives, the active components i...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Chan YK,Kwok HH,Chan LS,Leung KS,Shi J,Mak NK,Wong RN,Yue PY

    更新日期:2012-03-01 00:00:00

  • Dose-dependent regulation of mitochondrial function and cell death pathway by sorafenib in liver cancer cells.

    abstract::Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the fourth most frequent cause of cancer-related death worldwide. Sorafenib is the first line recommended therapy for patients with locally advanced/metastatic HCC. The low response rate is attributed to intrinsic resistance of HCC cell...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Rodríguez-Hernández MA,de la Cruz-Ojeda P,Gallego P,Navarro-Villarán E,Staňková P,Del Campo JA,Kučera O,Elkalaf M,Maseko TE,Červinková Z,Muntané J

    更新日期:2020-06-01 00:00:00

  • Characterization of the deamidase enzyme responsible for the metabolism of the anticancer peptide: H-Arg-D-Trp-NmePhe-D-Trp-Leu-Met-NH2.

    abstract::H-Arg-D-Trp-NmePhe-D-Trp-Leu-Met-NH2, a broad spectrum neuropeptide growth factor antagonist (antagonist G), is soon to enter a phase I clinical trial for the treatment of small-cell lung cancer (SCLC). The pre-clinical pharmacology of this peptide has revealed that its metabolism proceeds from the C-terminus via deam...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Jones DA,Cummings J,Langdon SP,MacLellan A,Smyth JF

    更新日期:1995-08-25 00:00:00

  • Sulfation of minoxidil by human liver phenol sulfotransferase.

    abstract::The N,O-sulfate of minoxidil (Mnx) is the active agent in producing the vasodilation and the hair-growth stimulating responses observed with Mnx treatment. In this report, Mnx sulfation activity was assayed in cytosol prepared from several normal human livers, and Mnx sulfation was shown to correlate significantly wit...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Falany CN,Kerl EA

    更新日期:1990-09-01 00:00:00

  • de novo synthesis of calmodulin binding protein in substance P-induced steroidogenesis in bovine adrenocortical cells.

    abstract::In order to clarify the mechanism of substance P (SP)-induced cortisol secretion from bovine adrenocortical (BAC) cells, protein synthesis at the early stage of SP-stimulation in BAC cells was investigated. Both SP and adrenocorticotropic hormone (ACTH) increased [3H]leucine uptake into BAC cells in a dose-dependent f...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Yoshida T,Mio M,Tasaka K

    更新日期:1992-10-06 00:00:00

  • Characterization of the muscarinic receptor subtype in isolated gastric fundic cells of the rabbit.

    abstract::The characteristics of the muscarinic receptor in isolated gastric fundic cells from rabbit were determined by radioligand binding techniques and functional tests. The dissociation constants (KDS) of selective (hexahydrosiladifenidol and pirenzepine) and non-selective (N-methylscopolamine and atropine) muscarinic rece...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Baudiere B,Monferini E,Giraldo E,Ladinsky H,Bali JP

    更新日期:1987-09-15 00:00:00

  • Different effects of oxytetracycline and doxycycline on mitochondrial protein synthesis in rat liver after long-term treatment.

    abstract::The tetracyclines inhibit specifically mitochondrial (mt) and bacterial protein synthesis when they are present in low concentrations (2-10 micrograms/ml). There is no difference between the various members of this group of antibiotics in this respect. In the present study, however, it is shown that the inhibitory eff...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: van den Bogert C,Holtrop M,Melis TE,Roefsema PR,Kroon AM

    更新日期:1987-05-01 00:00:00

  • Conversion of irinotecan (CPT-11) to its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), by human liver carboxylesterase.

    abstract::We have investigated the conversion of the novel anti-topoisomerase I agent CPT-11 (irinotecan; 7-ethyl-10[4-(1-piperidino)-1-piperidno]carbonyloxycamptothecin ) to its active metabolite, SN-38 (7-ethyl-10-hydroxycamptothecin), by human liver carboxylesterase (HLC). Production of SN-38 was relatively inefficient and w...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Rivory LP,Bowles MR,Robert J,Pond SM

    更新日期:1996-10-11 00:00:00

  • Increased glutathione in cultured hepatocytes associated with induction of cytochrome P-450. Lack of effect of glutathione depletion on induction of cytochrome P-450 and delta-aminolevulinate synthase.

    abstract::Cellular glutathione concentrations in primary cultures of chick embryo hepatocytes were 15.3 +/- 5.3 nmoles/mg protein (mean +/- S.D.) and remained stable for up to 3 days in culture. The presence of insulin was not essential for the maintenance of glutathione concentrations. Induction of cytochrome P-450 by phenobar...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Shedlofsky SI,Sinclair PR,Sinclair JF,Bonkovsky HL

    更新日期:1984-05-01 00:00:00

  • Molecular mechanisms underlying the anti-obesity potential of prunetin, an O-methylated isoflavone.

    abstract::Prunetin is an O-methylated isoflavone, which is a type of flavonoid. There are a limited number of reports detailing the biological activities of prunetin. Although an anti-inflammatory effect of prunetin has been reported in vitro, to our knowledge, there have been no reports on anti-adipogenic effects of prunetin i...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Ahn TG,Yang G,Lee HM,Kim MD,Choi HY,Park KS,Lee SD,Kook YB,An HJ

    更新日期:2013-05-15 00:00:00

  • Lipids, LXRs and prostate cancer: are HDACs a new link?

    abstract::Lipids play a complex role in prostate cancer (PCa). Increased de novo synthesis of fatty acids and/or cholesterol is associated with the development of prostate tumors. Liver X Receptors (LXRs) are members of the nuclear receptor family that regulates intracellular lipid homeostasis. Targeting the transcriptional act...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Hoang JJ,Baron S,Volle DH,Lobaccaro JM,Trousson A

    更新日期:2013-07-01 00:00:00

  • Modulation of SIRT1-mediated signaling cascades in the liver contributes to the amelioration of nonalcoholic steatohepatitis in high fat fed middle-aged LDL receptor knockout mice by dihydromyricetin.

    abstract::Dihydromyricetin (DMY) is the most abundant flavonoid in Ampelopsis grossedentata possessing many pharmacological activities. But less is known about its protective effect against nonalcoholic steatohepatitis (NASH) in the context of metabolic syndrome. The present study is aimed to evaluate the pharmacological effect...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Zeng Y,Hua YQ,Wang W,Zhang H,Xu XL

    更新日期:2020-05-01 00:00:00

  • Tricyclic antidepressant-induced lipidosis in human peripheral monocytes in vitro, as well as in a monocyte-derived cell line, as monitored by spectrofluorimetry and flow cytometry after staining with Nile red.

    abstract::Human mono- and lymphocytes from peripheral blood and the monoblastoid cell line U-937 were used in this in vitro study of drug-induced lipidosis. Mono- and lymphocytes were exposed for 4 days to three different tricyclic antidepressants (TCAs), imipramine (25 microM), clomipramine (10 microM) and citalopram (80 micro...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Xia Z,Appelkvist EL,DePierre JW,Nässberger L

    更新日期:1997-05-15 00:00:00

  • Indomethacin and glucocorticoid metabolism in rat liver cytosol.

    abstract::3 alpha-Hydroxysteroid dehydrogenase (EC of rat liver cytosol catalyzes the second step in glucocorticoid metabolism, namely the NADPH-dependent reduction of 5 beta-dihydrocortisol to tetrahydrocortisol. The purified enzyme is potently inhibited by the nonsteroidal anti-inflammatory drugs [Penning and Talala...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Penning TM

    更新日期:1986-12-01 00:00:00

  • Effect of culture conditions on the expression and function of Bsep, Mrp2, and Mdr1a/b in sandwich-cultured rat hepatocytes.

    abstract::Rat hepatocytes cultured in a sandwich configuration form functional canalicular networks. The influence of extracellular matrix configuration, medium composition, and confluency on the expression and function of Bsep, Mrp2, and Mdr1a/b in sandwich-cultured (SC) rat hepatocytes was examined. Primary rat hepatocytes we...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Turncliff RZ,Tian X,Brouwer KL

    更新日期:2006-05-14 00:00:00

  • Effects of dihydropyridine derivatives and anticonvulsant drugs on [3H]nitrendipine binding and calcium and sodium fluxes in brain.

    abstract::The binding of [3H]nitrendipine to rat cortical membranes was reduced by phenytoin, phenobarbital, and pentobarbital. The IC50 values were 0.09, 0.40, and 0.76 mM respectively. The drugs reduced the apparent binding affinity of [3H]nitrendipine with little effect on the maximum number of binding sites. The inhibitory ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Harris RA,Jones SB,Bruno P,Bylund DB

    更新日期:1985-06-15 00:00:00

  • Anti-fibrotic and anti-inflammatory properties of melatonin on human gingival fibroblasts in vitro.

    abstract::Melatonin (MEL) has been proposed as a therapeutic agent for the oral cavity, due to its antioxidant and anti-inflammatory effects since periodontal diseases are aggravated by free radicals, and by disproportionate immunological response to plaque microorganism. In addition, MEL promotes bone formation. This study aim...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Gómez-Florit M,Ramis JM,Monjo M

    更新日期:2013-12-15 00:00:00

  • Pyridine N-oxide derivatives inhibit viral transactivation by interfering with NF-kappaB binding.

    abstract::Pyridine N-oxide derivatives represent a new class of anti-HIV compounds for which some members exclusively inhibit HIV-1 RT, whereas other members act, additionally or alternatively, at a post-integrational event in the replicative cycle of HIV. A prototype pyridine N-oxide derivative, JPL-32, inhibited tumor necrosi...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Stevens M,Pannecouque C,De Clercq E,Balzarini J

    更新日期:2006-04-14 00:00:00

  • Quilamine HQ1-44, an iron chelator vectorized toward tumor cells by the polyamine transport system, inhibits HCT116 tumor growth without adverse effect.

    abstract::Tumor cell growth requires large iron quantities and the deprivation of this metal induced by synthetic metal chelators is therefore an attractive method for limiting the cancer cell proliferation. The antiproliferative effect of the Quilamine HQ1-44, a new iron chelator vectorized toward tumor cells by a polyamine ch...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Renaud S,Corcé V,Cannie I,Ropert M,Lepage S,Loréal O,Deniaud D,Gaboriau F

    更新日期:2015-08-01 00:00:00

  • Inhibitory effect of ionized free intracellular calcium enhanced by ruthenium red and m-chloro-carbonylcyanide phenyl hydrazon on the evoked release of acetylcholine.

    abstract::In order to understand the relationship between the free ionized calcium concentration in the axon terminals and the transmitter release we have investigated the effect of ruthenium red (RuR) and m-chloro-carbonylcyanide phenyl hydrazon (CCCP), mitochondrial uncoupler agents on the liberation of acetylcholine from mye...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Bernath S,Vizi ES

    更新日期:1987-11-01 00:00:00

  • Evidence for acyloxymethyl esters of pyrimidine 5'-deoxyribonucleotides as extracellular sources of active 5'-deoxyribonucleotides in cultured cells.

    abstract::Cells commonly resist growth inhibition by purine and pyrimidine bases and nucleosides by restricting intracellular formation of the corresponding 5'-mononucleotides. Nucleotide derivatives that can act as effective membrane-transport precursors of the poorly membrane-permeable nucleotides have not been identified so ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Freed JJ,Farquhar D,Hampton A

    更新日期:1989-10-01 00:00:00

  • Enhancement by beraprost sodium, a stable analogue of prostacyclin, in thrombomodulin expression on membrane surface of cultured vascular endothelial cells via increase in cyclic AMP level.

    abstract::Prostacyclin and beraprost sodium (beraprost), a stable analogue of prostacyclin, increased cyclic AMP (cAMP) levels of cultured human umbilical vein endothelial cells (HUVEC) in a concentration-dependent manner. The elevation of cAMP by beraprost was sustained longer than that by prostacyclin. The expression of throm...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kainoh M,Maruyama I,Nishio S,Nakadate T

    更新日期:1991-04-15 00:00:00

  • The imidazoline-like drug S23515 affects lipid metabolism in hepatocyte by inhibiting the oxidosqualene: lanosterol cyclase activity.

    abstract::Imidazoline-like drugs are centrally-acting antihypertensive agents that inhibit the activity of the sympathetic nervous system by interacting with the alpha2-adrenoreceptor and also with a non-adrenergic imidazoline binding site called the imidazoline 1 receptor. Recently, these molecules were proposed to play an add...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Venteclef N,Guillard R,Issandou M

    更新日期:2005-04-01 00:00:00