Search results for "Phosphorylation"

showing 10 items of 975 documents

Down-regulation of Glutathione and Bcl-2 Synthesis in Mouse B16 Melanoma Cells Avoids Their Survival during Interaction with the Vascular Endothelium

2003

B16 melanoma (B16M) cells with high GSH content show high metastatic activity. However, the molecular mechanisms linking GSH to metastatic cell survival are unclear. The possible relationship between GSH and the ability of Bcl-2 to prevent cell death was studied in B16M cells with high (F10) and low (F1) metastatic potential. Analysis of a Bcl-2 family of genes revealed that B16M-F10 cells, as compared with B16M-F1 cells, overexpressed preferentially Bcl-2 (approximately 5.7-fold). Hepatic sinusoidal endothelium-induced B16M-F10 cytotoxicity in vitro increased from approximately 19% (controls) to approximately 97% in GSH-depleted B16M-F10 cells treated with an antisense Bcl-2 oligodeoxynucl…

MaleProgrammed cell deathPore complexCell SurvivalMelanoma ExperimentalDown-RegulationOxidative phosphorylationBiologyBiochemistryOligodeoxyribonucleotides AntisenseMicechemistry.chemical_compoundDownregulation and upregulationCell Line TumorAnimalsButhionine SulfoximineMolecular BiologyBase SequenceTransition (genetics)Cell BiologyGlutathioneGlutathioneMolecular biologyGenes bcl-2Cell biologyMice Inbred C57BLOxidative StressCytosolchemistryEndothelium VascularEffluxCell DivisionJournal of Biological Chemistry
researchProduct

In vitro anti-inflammatory effects of AZD8999, a novel bifunctional muscarinic acetylcholine receptor antagonist /β2-adrenoceptor agonist (MABA) comp…

2019

Recent evidence indicates that AZD8999 (LAS190792), a novel muscarinic acetylcholine receptor antagonist and β2-adrenoceptor agonist (MABA) in development for chronic respiratory diseases, induces potent and sustained relaxant effects in human bronchi by adressing both muscarinic acetylcholine receptors and β2-adrenoceptor. However, the anti-inflammatory effects of the AZD8999 monotherapy or in combination with corticosteroids are unknown. This study investigates the anti-inflammatory effects of AZD8999 in monotherapy and combined with fluticasone propionate in neutrophils from healthy and chronic obstructive pulmonary disease (COPD) patients. Peripheral blood neutrophils from healthy and C…

MalePulmonologyNeutrophilsPhysiologyAnti-Inflammatory AgentsPharmacologyPathology and Laboratory MedicineBiochemistryPulmonary Disease Chronic ObstructiveWhite Blood CellsGlucocorticoid receptorAnimal CellsMuscarinic acetylcholine receptorMedicine and Health SciencesPost-Translational ModificationPhosphorylationReceptorImmune ResponseMultidisciplinaryPharmaceuticsQRDrug SynergismMiddle AgedReceptors MuscarinicHealthy VolunteersBody FluidsChemistryBloodPhysical SciencesQuinolinesMedicineDrug Therapy CombinationFemalemedicine.symptomCellular TypesAnatomymedicine.drugResearch ArticleSignal TransductionAgonistTransmembrane Receptorsmedicine.drug_classp38 mitogen-activated protein kinasesChronic Obstructive Pulmonary DiseaseImmune CellsScienceImmunologyInflammationMuscarinic AntagonistsThiophenesFluticasone propionateSigns and SymptomsDrug TherapyCyclohexanesDiagnostic MedicinemedicineHumansAdrenergic beta-2 Receptor AgonistsAgedInflammationBlood CellsDose-Response Relationship Drugbusiness.industryAntagonistChemical CompoundsBiology and Life SciencesProteinsCell BiologyAcetylcholine ReceptorsFluticasoneMuscarinic Acetylcholine ReceptorsReceptors Adrenergic beta-2PropionatesbusinessReceptor Antagonist TherapyPLoS ONE
researchProduct

Visible light (>395nm) causes micronuclei formation in mammalian cells without generation of cyclobutane pyrimidine dimers

2004

Solar radiation gives rise to DNA damage in mammalian cells not only directly by excitation of DNA, which generates predominantly pyrimidine dimers, but also indirectly by the excitation of endogenous photosensitizers, which causes oxidative DNA modifications. The latter mechanism has a low quantum yield, but it is the only one proceeding in the visible range of the spectrum. To investigate its relevance for the genotoxicity of sunlight, we have analysed the generation of micronuclei associated with the induction of oxidative DNA damage by visible light in melanoma cells and primary human skin fibroblasts. Similar yields of light-induced oxidative DNA base modifications sensitive to the rep…

MalePurineLightDNA damageHealth Toxicology and MutagenesisPyrimidine dimerOxidative phosphorylationmedicine.disease_causechemistry.chemical_compoundTumor Cells CulturedGeneticsmedicineAnimalsHumansMelanomaMolecular BiologyGeneticsMicronucleus TestsMiddle AgedchemistryPyrimidine DimersDNA glycosylaseMicronucleus testBiophysicsDNAGenotoxicityMutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
researchProduct

Carboxyamidotriazole-Orotate Inhibits the Growth of Imatinib-Resistant Chronic Myeloid Leukaemia Cells and Modulates Exosomes-Stimulated Angiogenesis

2012

The Bcr/Abl kinase has been targeted for the treatment of chronic myelogenous leukaemia (CML) by imatinib mesylate. While imatinib has been extremely effective for chronic phase CML, blast crisis CML are often resistant. New therapeutic options are therefore needed for this fatal disease. Although more common in solid tumors, increased microvessel density was also reported in chronic myelogenous leukaemia and was associated with a significant increase of angiogenic factors, suggesting that vascularity in hematologic malignancies is a controlled process and may play a role in the leukaemogenic process thus representing an alternative therapeutic target. Carboxyamidotriazole-orotate (CTO) is …

MaleResearch ValidityPhysiologyAngiogenesisTumor PhysiologyFusion Proteins bcr-ablCancer Treatmentlcsh:MedicinePharmacologyExosomesCardiovascular PhysiologyBiochemistryPiperazinesHematologic Cancers and Related DisordersMicechemistry.chemical_compoundCell Movementhemic and lymphatic diseasesMolecular Cell BiologyBasic Cancer ResearchMedicine and Health SciencesPhosphorylationPost-Translational ModificationExtracellular Signal-Regulated MAP Kinaseslcsh:ScienceChronic Myelogenous LeukemiaMultidisciplinaryABLNeovascularization PathologicGene Expression Regulation LeukemicChemistryHematologyResearch AssessmentOncologyBenzamidesImatinib MesylateMedicineOncology AgentsAntiangiogenesis Therapymedicine.drugResearch ArticleChronic Myeloid LeukemiaAntineoplastic AgentsResearch and Analysis MethodsCell GrowthCell Line TumorLeukemia Myelogenous Chronic BCR-ABL PositiveLeukemiasCell AdhesionHuman Umbilical Vein Endothelial CellsmedicineAnimalsHumansRNA MessengerPhosphotyrosineBiologyCell ProliferationOrotic AcidTumor microenvironmentCarboxyamidotriazoleInterleukin-8lcsh:RBiology and Life SciencesProteinsCancers and NeoplasmsImatinibTriazolesmedicine.diseaseXenograft Model Antitumor AssaysRetractionExosomePyrimidinesImatinib mesylateDrug Resistance NeoplasmCarboxyamidotriazole Orotatelcsh:QAngiogenesisCell Adhesion MoleculesProto-Oncogene Proteins c-aktDevelopmental BiologyChronic myelogenous leukemiaPLoS ONE
researchProduct

Retrograde neurotrophic signaling in rat retinal ganglion cells is transmitted via the ERK5 but not the ERK1/2 pathway.

2014

Purpose Neurotrophic deprivation is considered an important event in glaucomatous retinal ganglion cell (RGC) death. However, the mitogen-activated protein kinase (MAPK) pathway transmitting axonal neurotrophic signals in RGC has not been identified. We investigated the involvement of ERK5 and ERK1/2 in retrograde axonal neurotrophic signaling in rats. Methods Adult Sprague-Dawley rats were used. Retinal immunostaining for ERK5 and MEK5 was performed. Levels of total and phosphorylated ERK5 and ERK1/2 were analyzed in retinal lysate by quantitative Western blotting. The effects of age, brain-derived neurotrophic factor (BDNF) stimulation at RGC soma (intravitreal injection) or axon ending (…

MaleRetinal Ganglion Cellsmedicine.medical_specialtyAgingSuperior ColliculiMAP Kinase Signaling SystemBlotting WesternRetinal ganglionRetinaRats Sprague-Dawley03 medical and health sciences0302 clinical medicineNeurotrophic factorsInternal medicinemedicineAnimalsAxonPhosphorylationMitogen-Activated Protein Kinase 7030304 developmental biologyBrain-derived neurotrophic factorMitogen-Activated Protein Kinase 10303 health sciencesRetinaMitogen-Activated Protein Kinase 3biologyChemistryBrain-Derived Neurotrophic FactorBrainAnatomyRatsmedicine.anatomical_structureEndocrinologynervous systemRetinal ganglion cellTrk receptorOptic Nerve InjuriesIntravitreal Injectionsbiology.proteinsense organsNeuroglia030217 neurology & neurosurgeryNeurotrophinInvestigative ophthalmologyvisual science
researchProduct

IL-6 receptor independent stimulation of human gp130 by viral IL-6.

2000

Abstract The genome of human herpes virus 8, which is associated with Kaposi’s sarcoma, encodes proteins with similarities to cytokines and chemokines including a homologue of IL-6. Although the function of these viral proteins is unclear, they might have the potential to modulate the immune system. For viral IL-6 (vIL-6), it has been demonstrated that it stimulates IL-6-dependent cells, indicating that the IL-6R system is used. IL-6 binds to IL-6R, and the IL-6/IL-6R complex associates with gp130 which dimerizes and initiates intracellular signaling. Cells that only express gp130 but no IL-6R cannot be stimulated by IL-6 unless a soluble form of the IL-6R is present. This type of signaling…

MaleSTAT3 Transcription FactorChemokinemedicine.medical_treatmentImmunologyGenetic VectorsBiologylaw.inventionViral ProteinsImmune systemlawAntigens CDmedicineCytokine Receptor gp130Tumor Cells CulturedImmunology and AllergyAnimalsChemical PrecipitationHumansCloning MolecularPhosphorylationInterleukin 6Sarcoma KaposiAgedMembrane GlycoproteinsInterleukin-6Glycoprotein 130Receptors Interleukin-6Growth InhibitorsRecombinant ProteinsCell biologyDNA-Binding ProteinsCytokineInterleukin-6 receptorCOS CellsRecombinant DNAbiology.proteinTrans-ActivatorsIntracellularProtein BindingSignal TransductionJournal of immunology (Baltimore, Md. : 1950)
researchProduct

In vivo GSH depletion induces c-myc expression by modulation of chromatin protein complexes.

2009

Abstract We hypothesize that glutathione (GSH) fluctuations could have a prominent role in the modulation of c-myc expression through a mechanism affecting chromatin remodeling complexes. This could lead to an open chromatin structure accessible to transcription factors. We studied the in vivo effect of GSH depletion on these complexes bound to the c-myc promoter in the liver of l-buthionine-(S,R)-sulfoximine (BSO)-treated rats. Using chromatin immunoprecipitation we found that 3 h after BSO treatment the repressing complexes Id2 and Sin3A (part of a histone–deacetylase complex) were released from the c-myc promoter. STAT3 was phosphorylated and associated with its coactivator p300 with int…

MaleSTAT3 Transcription FactorTranscriptional ActivationTime FactorsBiologyBiochemistryChromatin remodelingHistone DeacetylasesProto-Oncogene Proteins c-mycHistone H3Physiology (medical)Gene expressionCoactivatorTranscriptional regulationAnimalsp300-CBP Transcription FactorsPhosphorylationRats WistarTranscription factorButhionine SulfoximineInhibitor of Differentiation Protein 2AcetylationChromatin Assembly and DisassemblyMolecular biologyGlutathioneChromatinRatsRepressor ProteinsSin3 Histone Deacetylase and Corepressor ComplexGene Expression RegulationLiverChromatin immunoprecipitationProtein BindingFree radical biologymedicine
researchProduct

Anti-inflammatory and joint protective effects of extra-virgin olive-oil polyphenol extract in experimental arthritis

2014

The consumption of extra virgin olive oil (EVOO) in Mediterranean countries has shown beneficial effects. A wide range of evidence indicates that phenolic compounds present in EVOO are endowed with anti-inflammatory properties. In this work, we evaluated the effects of EVOO-polyphenol extract (PE) in a model of rheumatoid arthritis, the collagen-induced arthritis model in mice. On day 0, DBA-1/J mice were immunized with bovine type II collagen. On day 21, mice received a booster injection. PE (100 and 200 mg/kg) was orally administered once a day from days 29 to 41 to arthritic mice. We have demonstrated that PE decreases joint edema, cell migration, cartilage degradation and bone erosion. …

MaleSTAT3 Transcription Factormedicine.drug_classEndocrinology Diabetes and Metabolismmedicine.medical_treatmentClinical BiochemistryAnti-Inflammatory AgentsType II collagenAdministration OralDown-RegulationArthritisPharmacologyp38 Mitogen-Activated Protein KinasesBiochemistryDinoprostoneAnti-inflammatoryProinflammatory cytokineMiceEdemamedicineAnimalsPlant OilsPhosphorylationProstaglandin E2Olive OilMolecular BiologyProstaglandin-E SynthasesActivating Transcription Factor 3Nutrition and DieteticsChemistryJNK Mitogen-Activated Protein KinasesNF-kappa BPolyphenolsmedicine.diseaseArthritis ExperimentalIntramolecular OxidoreductasesCyclooxygenase 2Mice Inbred DBARheumatoid arthritisImmunologyCytokinesmedicine.symptomSignal TransductionProstaglandin Emedicine.drugThe Journal of Nutritional Biochemistry
researchProduct

The interleukin (IL)-31/IL-31R axis contributes to tumor growth in human follicular lymphoma

2014

Interleukin (IL)-31A binds to an heterodimer composed of IL-31 receptor A (IL-31RA) and Oncostatin M Receptor (OSMR). The IL-31/IL-31R complex is involved in the pathogenesis of various skin diseases, including cutaneous T-cell lymphoma. No information is available on the relations between the IL-31/IL-31R complex and B-cell lymphoma. Here we have addressed this issue in follicular lymphoma (FL), a prototypic germinal center(GC)-derived B-cell malignancy. IL-31 enhanced primary FL cell proliferation through IL-31R-driven signal transducer and activator of transcription factor 1/3 (STAT1/3), extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation. In contrast, GC B cells d…

MaleSTAT3 Transcription Factormedicine.medical_specialtyCancer ResearchPrimary Cell CultureFollicular lymphomaBiologyParacrine signallingCytosolCell-Derived MicroparticlesInternal medicinemedicineHumansProtein IsoformsPhosphorylationAutocrine signallingLymphoma FollicularCell ProliferationMitogen-Activated Protein Kinase 1B-LymphocytesMitogen-Activated Protein Kinase 3Gene Expression Regulation LeukemicInterleukinsMicrovesicleMedicine (all)Cell MembraneB-LymphocyteGerminal centerOncostatin M receptorInterleukinProtein IsoformReceptors InterleukinHematologyInterleukinMiddle Agedmedicine.diseaseGerminal CenterMolecular biologyCell-Derived MicroparticleEndocrinologySTAT1 Transcription FactorAnesthesiology and Pain MedicineOncologyFemaleSignal transductionNeoplasm GradingProto-Oncogene Proteins c-aktHumanSignal Transduction
researchProduct

Modulation of the control of mutagenic metabolites derived from cyclophosphamide and ifosfamide by stimulation of protein kinase A

1990

The phosphorylation of the 2 major phenobarbital-inducible cytochrome P450 isoenzymes IIB1 and IIB2 was increased in intact hepatocytes by the action of the membrane-permeating cAMP derivative N6,O2'-dibutyryl-cAMP. Under these conditions cyclophosphamide and ifosfamide (which are known to be activated by cytochrome P450 IIB1) were investigated for mutagenicity in Salmonella typhimurium TA1535 and TA100 and for cytotoxicity in TA1535. Cyclophosphamide and ifosfamide were transformed to mutagenic and cytotoxic metabolites by the hepatocytes. The activation of both drugs to mutagens was markedly reduced after pretreatment of the hepatocytes with the membrane-permeating cAMP derivative N6,O2'-…

MaleSalmonella typhimuriumCyclophosphamideHealth Toxicology and MutagenesisMetaboliteStimulationIn Vitro TechniquesPharmacologychemistry.chemical_compoundCytochrome P-450 Enzyme SystemTheophyllineGeneticsmedicineAnimalsTheophyllineIfosfamidePhosphorylationProtein kinase ACyclophosphamideMolecular BiologyIfosfamidebiologyCytochrome P450Rats Inbred StrainsRatsIsoenzymesBucladesineLiverchemistrybiology.proteinPhenobarbitalProtein KinasesMutagensmedicine.drugMutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
researchProduct