Multiple effects of staurosporine, a kinase inhibitor, on thymocyte functions. Comparison with the effect of tyrosine kinase inhibitors.


:The effects of staurosporine, a protein kinase inhibitor, on the signal transduction and proliferation of thymocytes were studied. Signal transduction in response to Concanavalin A (Con A) as well as Concanavalin A (Con A)-induced augmentation of [3H]inositol incorporation into phospholipids were inhibited by staurosporine (> or = 10(-8) M). Staurosporine inhibited thymocyte proliferation in response to Con A in the presence or absence of the phorbol ester, phorbol myristate acetate (TPA) (10 nM). This inhibition was observed regardless of whether staurosporine was added together with Con A or 3 hr later. High concentrations of staurosporine (> 10(-8) M) inhibited thymocyte proliferation induced by the calcium ionophore A23187 and the phorbol ester TPA, whereas lower concentrations of the inhibitor (< or = 10(-8) M) enhanced thymidine incorporation in response to these activators. This dual effect of staurosporine was also observed in the presence of the staurosporine-related kinase inhibitor, K252a. In contrast, the tyrosine kinase inhibitor, tyrphostin AG490, inhibited the response to A23187 and TPA at all concentrations of the inhibitor and no augmentation was seen. Interleukin 2 (IL-2)-driven mitogenesis in IL-2-dependent cells was also inhibited by staurosporine. We suggest that the inhibition of thymocyte proliferation by staurosporine results from inhibition of both protein kinase C and tyrosine kinase: the augmentation of the response to A23187 and TPA results from inhibition of protein kinase C. Inhibition of signal transduction as well as inhibition of IL-2-driven mitogenesis result from inhibition of tyrosine kinase.


Biochem Pharmacol


Biochemical pharmacology


Zilberman Y,Gutman Y




Has Abstract


1992-10-20 00:00:00














  • Contribution of different phospholipases and arachidonic acid metabolites in the response of gallbladder smooth muscle to cholecystokinin.

    abstract::Guinea pig gallbladder muscle strips were used to investigate the contribution of different sources of diacylglicerol (DAG) in the cholecystokinin (CCK)-induced contraction. The involvement of arachidonic acid (AA) in this response was also investigated. Three distinct pathways for DAG production were investigated wit...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Alcón S,Morales S,Camello PJ,Pozo MJ

    更新日期:2002-10-01 00:00:00

  • Regulation on SIRT1-PGC-1α/Nrf2 pathway together with selective inhibition of aldose reductase makes compound hr5F a potential agent for the treatment of diabetic complications.

    abstract::(R,E)-N-(3-(2-acetamido-3-(benzyloxy) propanamido)propyl)-2-cyano-3-(4-hydroxy phenyl)acrylamide (hr5F) was design-synthesized based on bioactivity focus strategy as a potential agent to treat diabetic complicates. With in vitro enzyme assay, it is confirmed that hr5F is an effective ALR2 inhibitor with IC50 value of ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Wang Z,Yuan S,Li Y,Zhang Z,Xiao W,Tang D,Ye K,Liu Z,Wang C,Zheng Y,Nie H,Chen H

    更新日期:2018-04-01 00:00:00

  • Antagonistic effect of the cardioprotector (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF-187) on DNA breaks and cytotoxicity induced by the topoisomerase II directed drugs daunorubicin and etoposide (VP-16).

    abstract::The effect of the bisdioxopiperazine cardioprotector ICRF-187 (ADR-529, dexrazoxan) on drug-induced DNA damage and cytotoxicity was studied. Using alkaline elution assays, ICRF-187 in a dose-dependent manner inhibited the formation of DNA single strand breaks (SSBs) as well as DNA-protein cross-links induced by drugs ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Sehested M,Jensen PB,Sørensen BS,Holm B,Friche E,Demant EJ

    更新日期:1993-08-03 00:00:00

  • Inhibition by the protein kinase inhibitor HA1077 of the activation of NADPH oxidase in human neutrophils.

    abstract::The effect of an inhibitor of protein kinase, HA1077 [1-(5-isoquinolinesulfonyl)-homopiperazine HCl], and its hydroxylated metabolite, HA1100, on the activation of NADPH oxidase in human neutrophils were studied. Cells were preincubated with each drug for 10 min and then activated by treatment with phorbol myristate a...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Arai M,Sasaki Y,Nozawa R

    更新日期:1993-10-19 00:00:00

  • Inducibility of P450Coh by pyrazole and its derivatives.

    abstract::Pyrazole and several of its derivatives increase the hepatic microsomal coumarin 7-hydroxylase to a variable extent. The strongest inducers are pyrazole itself and those derivatives which have a hydroxy group or a halogen at the 4-position of the molecule. The increase in coumarin 7-hydroxylase is due to an increase i...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kojo A,Heiskanen R,Rytkönen AL,Honkakoski P,Juvonen R,Lang M

    更新日期:1991-10-09 00:00:00

  • SMAD-oncoprotein interplay: Potential determining factors in targeted therapies.

    abstract::The Transforming Growth Factor-β (TGF-β) signaling pathway plays a versatile role in diverse physiological and disease conditions. Outcomes of TGF-β signaling are divergent, sometimes even opposite, on cellular functions and disease progression through context-dependent transcriptional programs. For example, TGF-β sig...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Li X,Feng XH

    更新日期:2020-10-01 00:00:00

  • Development of resistance to photodynamic therapy (PDT) in human breast cancer cells is photosensitizer-dependent: Possible mechanisms and approaches for overcoming PDT-resistance.

    abstract::Here we report on the induction of resistance to photodynamic therapy (PDT) in the ABCG2-high human breast cancer cell line MA11 after repetitive PDT, using either Pheophorbide A (PhA) or di-sulphonated meso-tetraphenylchlorin (TPCS2a) as photosensitizer. Resistance to PhA-PDT was associated with enhanced expression o...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Olsen CE,Weyergang A,Edwards VT,Berg K,Brech A,Weisheit S,Høgset A,Selbo PK

    更新日期:2017-11-15 00:00:00

  • Akt activation protects pancreatic beta cells from AMPK-mediated death through stimulation of mTOR.

    abstract::Sustained activation of AMP-activated protein kinase (AMPK) induces apoptosis in several cell types. In pancreatic beta cells this occurs under glucose limitation, or in the presence of the pharmacological AMPK activator 5-aminoimidazole-4-carboxamide-riboside (AICAR). It is unknown whether Akt activation can countera...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Cai Y,Wang Q,Ling Z,Pipeleers D,McDermott P,Pende M,Heimberg H,Van de Casteele M

    更新日期:2008-05-15 00:00:00

  • PI3K/AKT/mTOR signaling as a molecular target in head and neck cancer.

    abstract::The aim of this review is to summarize current available information about the role of PI3K/AKT/mTOR signaling in head and neck cancer as a potential target for new therapy options. 90% of all head and neck cancers are squamous cell carcinomas (HNSCC). The most common genetic alteration is inactivation of p16 gene whi...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Marquard FE,Jücker M

    更新日期:2020-02-01 00:00:00

  • Radiolabelling of the human 5-HT2A receptor with an agonist, a partial agonist and an antagonist: effects on apparent agonist affinities.

    abstract::Previous work has shown that 5-hydroxytryptamine (5-HT)2A receptors can be radiolabelled with various radioligands, including partial agonists, such as [125I]-DOI and [3H]-DOB, and antagonists, such as [3H]-ketanserin and [3H]-spiperone. Because 5-HT has high affinity for the 5-HT2A receptor when displacing [3H]-DOB, ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Sleight AJ,Stam NJ,Mutel V,Vanderheyden PM

    更新日期:1996-01-12 00:00:00

  • The lack of correlation between toxicity and free radical formation of two diaziridinyl benzoquinones.

    abstract::L1210 and K562 leukaemic cells have been used to study the relationship between cytotoxicity and free radical production by two aziridinyl benzoquinones, 2,5-bis(carboethoxyamino)3,6-diaziridinyl-1,4-benzoquinone (AZQ) and 2,5-bis(2-hydroxyethylamino)-3,6-diaziridinyl-1,4-benzoquinone (BZQ). BZQ showed a high level of...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Lea JS,Garner HJ,Butler J,Hoey BM,Ward TH

    更新日期:1988-05-15 00:00:00

  • Glucose metabolism and hemoglobin reactivity in human red blood cells exposed to the tryptophan metabolites 3-hydroxyanthranilate, quinolinate and picolinate.

    abstract::Glucose metabolism and hemoglobin reactivity in intact human erythrocytes were assessed in the presence of the tryptophan metabolites, 3-hydroxyanthranilate (3-HAT), quinolinate and picolinate. Of these compounds, only 3-HAT altered red cell oxidative status by inducing, in a dose-dependent manner, formation of methem...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Dykens JA,Sullivan SG,Stern A

    更新日期:1989-05-15 00:00:00

  • The bone marrow microenvironment as a sanctuary for minimal residual disease in CML.

    abstract::Bcr-abl kinase inhibitors have provided proof of principal that targeted therapy holds great promise for the treatment of cancer. However, despite the success of these agents in treating chronic myelogenous leukemia (CML), the majority of patients continue to present with minimal residual disease contained within the ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Nair RR,Tolentino J,Hazlehurst LA

    更新日期:2010-09-01 00:00:00

  • A 62 kDa protein is photoaffinity labelled by [3H]felodipine in vascular smooth muscle, but not in cardiac and skeletal muscle.

    abstract::Irradiation of a cytosolic fraction from vascular smooth muscle in the presence of [3H]felodipine resulted in the labelling of a protein with an apparent molecular weight of 62 kDa. The labelling was seen on UV-irradiation at 360 nm, but not at 254, 278 or at wavelengths above 410 nm. The photolabelling was enhanced i...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Nilsson A,Westerlund C,Boström S

    更新日期:1989-12-01 00:00:00

  • Ultrastructural morphology and localisation of cisplatin-induced platinum-DNA adducts in a cisplatin-sensitive and -resistant human small cell lung cancer cell line using electron microscopy.

    abstract::Ultrastructural morphology (transmission electron microscopy) and localisation of cisplatin-induced platinum (Pt)-DNA adducts (immunoelectron microscopy) were analysed in the human small cell lung cancer cell line GLC(4) and its 40-fold in vitro acquired cisplatin-resistant subline GLC(4)-CDDP, which is characterised ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Meijera C,van Luyn MJ,Nienhuis EF,Blom N,Mulder NH,de Vries EG

    更新日期:2001-03-01 00:00:00

  • Novel modified adenosine 5'-triphosphate analogues pharmacologically characterized in human embryonic kidney 293 cells highly expressing rat brain P2Y(1) receptor: Biotinylated analogue potentially suitable for specific P2Y(1) receptor isolation.

    abstract::Rat brain P2Y(1) (rP2Y(1)) receptor-transfected human embryonic kidney cells (HEK 293) were recently shown to have enhanced reactivity to both ATP and ADP (Vöhringer C, Schäfer R, Reiser G. Biochem Pharmacol 2000;59:791-800). Here, we demonstrated the usefulness of this cell line as a system for further studying novel...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Zündorf G,Schäfer R,Vöhringer C,Halbfinger E,Fischer B,Reiser G

    更新日期:2001-05-15 00:00:00

  • Comparison of the effect of isobutylmethylxanthine and phosphodiesterase-selective inhibitors on cAMP levels in SH-SY5Y neuroblastoma cells.

    abstract::A comparison of the effects of various phosphodiesterase (PDE) inhibitors upon cellular cAMP levels was undertaken in human neuroblastoma SH-SY5Y cells. When inhibitors such as rolipram and Ro 20 1724 (selective for the low Km cAMP-specific PDE) were used, cAMP levels were seen to rise dramatically under basal (< or =...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Morgan AJ,Murray KJ,Challiss RA

    更新日期:1993-06-22 00:00:00

  • Comparative expression of two alpha class glutathione S-transferases in human adult and prenatal liver tissues.

    abstract::The ability of the fetus to detoxify transplacental drugs and chemicals can be a critical determinant of teratogenesis and developmental toxicity. Developmentally regulated expression of alpha class glutathione S-transferases (GSTs) is of particular interest, since these isozymes have high activity toward peroxidative...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Gallagher EP,Gardner JL

    更新日期:2002-06-01 00:00:00

  • Subcellular localization of the camptothecin analogues, topotecan and gimatecan.

    abstract::Lipophilicity of camptothecins derivatives has been reported to improve the stability of the lactone ring and to favor rapid uptake and intracellular accumulation. Recently, a novel series of lipophilic camptothecins substituted at position 7 was developed, and gimatecan (ST1481) was selected for clinical development ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Croce AC,Bottiroli G,Supino R,Favini E,Zuco V,Zunino F

    更新日期:2004-03-15 00:00:00

  • Synergistic interaction of a chloroquine metabolite with chloroquine against drug-resistant malaria parasites.

    abstract::We have previously shown that structural modification of chlorpromazine to introduce a basic side chain converts this chloroquine (CQ) resistance-reversing agent into a compound that has activity against Plasmodium falciparum in vitro. In an effort to further dissect the structural features that determine quinoline an...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kalkanidis M,Klonis N,Tschan S,Deady LW,Tilley L

    更新日期:2004-04-01 00:00:00

  • Current perspectives on parathyroid hormone (PTH) and PTH-related protein (PTHrP) as bone anabolic therapies.

    abstract::Osteoporosis is characterized by low bone mineral density and/or poor bone microarchitecture leading to an increased risk of fractures. The skeletal alterations in osteoporosis are a consequence of a relative deficit of bone formation compared to bone resorption. Osteoporosis therapies have mostly relied on antiresorp...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Esbrit P,Alcaraz MJ

    更新日期:2013-05-15 00:00:00

  • Kynurenic acid inhibits glutamatergic transmission to CA1 pyramidal neurons via α7 nAChR-dependent and -independent mechanisms.

    abstract::Glutamatergic hypofunction and elevated levels of kynurenic acid (KYNA) in the brain are common features of patients with schizophrenia. In vivo studies indicate that in the hippocampus KYNA decreases glutamate levels, presumably via inhibition of α7 nicotinic receptors (nAChRs). Here we tested the hypothesis that bas...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Banerjee J,Alkondon M,Albuquerque EX

    更新日期:2012-10-15 00:00:00

  • Recovery after hypoglycemic brain injury. Action of some biological substances on the cerebral metabolism.

    abstract::In artificially ventilated beagle dogs a severe hypoglycemic condition was induced by insulin injection, while the posthypoglycemic recovery was induced by glucose treatment at the end of a 20-min period of spontaneous electroencephalographic silence. The motor area of the cerebral cortex was analyzed for glycolytic m...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Benzi G,Gorini A,Dossena M,Taglietti M,Fulle D,Pastoris O

    更新日期:1983-03-15 00:00:00

  • Relative contribution of rat cytochrome P450 isoforms to the metabolism of caffeine: the pathway and concentration dependence.

    abstract::The aim of the present study was to estimate the relative contribution of rat P450 isoforms to the metabolism of caffeine and to assess the usefulness of caffeine as a marker substance for estimating the activity of P450 in rat liver and its potential for pharmacokinetic interactions in pharmacological experiments. Th...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kot M,Daniel WA

    更新日期:2008-04-01 00:00:00

  • Mechanisms of accumulation of tyramine, metaraminol, and isoproterenol in isolated chromaffin granules and ghosts.

    abstract::The effects of the transmembrane pH gradient (delta pH) and the transmembrane potential gradient (delta psi) on the uptake of several sympathomimetic amines were investigated, using bovine adrenal chromaffin granules isolated in isotonic sucrose. As previously described [R. Johnson and A. Scarpa, J. Biol. Chem. 254 37...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Johnson RG,Carty SE,Hayflick S,Scarpa A

    更新日期:1982-03-01 00:00:00

  • Inhibition of EGFR pathway promotes the cytotoxicity of ABT-263 in human leukemia K562 cells by blocking MCL1 upregulation.

    abstract::ABT-263 induces MCL1 upregulation in cancer cells, which confers resistance to the drug. An increased understanding of the mechanism underlying ABT-263-induced MCL1 expression may provide a strategy to improve its tumor-suppression activity. The present study revealed that ABT-263 reduced the turnover of MCL1 mRNA, th...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Lee YC,Wang LJ,Huang CH,Chiou JT,Shi YJ,Chang LS

    更新日期:2020-08-01 00:00:00

  • Involvement of tumor necrosis factor (TNF)-alpha in phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin edema in mice.

    abstract::Topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse ear induced a prolonged skin inflammation. Histological analysis revealed that the early stage (approximately 3 h) and later stage (6-24 h) of the skin reaction are characterized by dermal edema and cell accumulation, respectively. Topical appl...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Murakawa M,Yamaoka K,Tanaka Y,Fukuda Y

    更新日期:2006-04-28 00:00:00

  • Benzylamine metabolism at low O2 concentrations. Relative sensitivities of monoamine oxidase, aldehyde dehydrogenase and hippurate synthesis to hypoxia.

    abstract::The O2 dependence of the metabolism of benzylamine to benzaldehyde, benzoate and hippurate was studied in isolated rat hepatocytes. The initial oxidation to benzaldehyde, catalyzed by monoamine oxidase, had an apparent Kmo2 value of 34 microM in cells and 40 microM in isolated rat liver mitochondria. The conversion of...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Jones DP

    更新日期:1984-02-01 00:00:00

  • Targeting cancer stem cells for more effective therapies: Taking out cancer's locomotive engine.

    abstract::Novel therapies for the treatment of solid tumors have generally failed to improve patient overall survival. These therapeutic approaches are typically focused on targeting signaling pathways implicated in cell growth and/or survival in order to shrink the malignant mass and achieve an objective clinical response; how...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Winquist RJ,Boucher DM,Wood M,Furey BF

    更新日期:2009-08-15 00:00:00

  • Critical roles of AMP-activated protein kinase in the carcinogenic metal-induced expression of VEGF and HIF-1 proteins in DU145 prostate carcinoma.

    abstract::Epidemiological and experimental animal data indicate that exposure to both metals and metalloid species exacerbates the risk of human diseases, particularly cancers. Vascular endothelial growth factor (VEGF), which performs a primary function in both tumor progression and angiogenesis, is up-regulated due to exposure...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Lee M,Hwang JT,Yun H,Kim EJ,Kim MJ,Kim SS,Ha J

    更新日期:2006-06-28 00:00:00