Millipore Sigma Vibrant Logo
 

cell


11686 Results Búsqueda avanzada  
Mostrar
Productos (889)
Documentos (9,926)
Páginas (871)

Acote sus resultados Utilice los filtros siguientes para refinar su búsqueda

Tipo de documento

  • (8,916)
  • (676)
  • (108)
  • (96)
  • (40)
  • Mostrar más
¿No encuentra lo que está buscando?
Póngase en contacto con
el Servicio de Atención
al Cliente

 
¿Necesita ayuda para encontrar un documento?

  • Cell 21962515

    Protein tyrosine phosphatase 1B (PTP1B) plays important roles in downregulation of insulin and leptin signaling and is an established therapeutic target for diabetes and obesity. PTP1B is regulated by reactive oxygen species (ROS) produced in response to various stimuli, including insulin. The reversibly oxidized form of the enzyme (PTP1B-OX) is inactive and undergoes profound conformational changes at the active site. We generated conformation-sensor antibodies, in the form of single-chain variable fragments (scFvs), that stabilize PTP1B-OX and thereby inhibit its phosphatase function. Expression of conformation-sensor scFvs as intracellular antibodies (intrabodies) enhanced insulin-induced tyrosyl phosphorylation of the β subunit of the insulin receptor and its substrate IRS-1 and increased insulin-induced phosphorylation of PKB/AKT. Our data suggest that stabilization of the oxidized, inactive form of PTP1B with appropriate therapeutic molecules may offer a paradigm for phosphatase drug development.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MABS456
    Nombre del producto:
    Anti-PTP1B Antibody (Oxidized), clone scFvs 45

  • Neural cell adhesion molecule-secreting transgenic mice display abnormalities in GABAergic interneurons and alterations in behavior. 15872114

    The extracellular region of the transmembrane neural cell adhesion molecule (NCAM-EC) is shed as a soluble fragment at elevated levels in the schizophrenic brain. A novel transgenic mouse line was generated to identify consequences on cortical development and function of expressing soluble NCAM-EC from the neuron-specific enolase promoter in the developing and mature neocortex and hippocampus. NCAM-EC transgenic mice exhibited a striking reduction in synaptic puncta of GABAergic interneurons in the cingulate, frontal association cortex, and amygdala but not hippocampus, as shown by decreased immunolabeling of glutamic acid decarboxylase-65 (GAD65), GAD67, and GABA transporter 1. Interneuron cell density was unaltered in the transgenic mice. Affected subpopulations of interneurons included basket interneurons evident in NCAM-EC transgenic mice intercrossed with a reporter line expressing green fluorescent protein and by parvalbumin staining. In addition, there appeared to be a reduction in excitatory synapses, as revealed by synaptophysin staining and apical dendritic spine density of cortical pyramidal cells. Behavioral analyses demonstrated higher basal locomotor activity of NCAM-EC mice and enhanced responses to amphetamine and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate compared with wild-type controls. Transgenic mice were deficient in prepulse inhibition, which was restored by clozapine but not by haloperidol. Additionally, NCAM-EC mice were impaired in contextual and cued fear conditioning. These results suggested that elevated shedding of NCAM perturbs synaptic connectivity of GABAergic interneurons and produces abnormal behaviors that may be relevant to schizophrenia and other neuropsychiatric disorders.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB5032
    Nombre del producto:
    Anti-Neural Cell Adhesion Molecule Antibody

  • Targeting translocator protein (18 kDa) (TSPO) dampens pro-inflammatory microglia reactivity in the retina and protects from degeneration. 26527153

    Reactive microglia are commonly seen in retinal degenerative diseases, and neurotoxic microglia responses can contribute to photoreceptor cell death. We and others have previously shown that translocator protein (18 kDa) (TSPO) is highly induced in retinal degenerations and that the selective TSPO ligand XBD173 (AC-5216, emapunil) exerts strong anti-inflammatory effects on microglia in vitro and ex vivo. Here, we investigated whether targeting TSPO with XBD173 has immuno-modulatory and neuroprotective functions in two mouse models of acute retinal degeneration using bright white light exposure.BALB/cJ and Cx3cr1(GFP/+) mice received intraperitoneal injections of 10 mg/kg XBD173 or vehicle for five consecutive days, starting 1 day prior to exposure to either 15,000 lux white light for 1 h or 50,000 lux focal light for 10 min, respectively. The effects of XBD173 treatment on microglia and Müller cell reactivity were analyzed by immuno-stainings of retinal sections and flat mounts, fluorescence-activated cell sorting (FACS) analysis, and mRNA expression of microglia markers using quantitative real-time PCR (qRT-PCR). Optical coherence tomography (OCT), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stainings, and morphometric analyses were used to quantify the extent of retinal degeneration and photoreceptor apoptosis.Four days after the mice were challenged with bright white light, a large number of amoeboid-shaped alerted microglia appeared in the degenerating outer retina, which was nearly completely prevented by treatment with XBD173. This treatment also down-regulated the expression of TSPO protein in microglia but did not change the TSPO levels in the retinal pigment epithelium (RPE). RT-PCR analysis showed that the microglia/macrophage markers Cd68 and activated microglia/macrophage whey acidic protein (Amwap) as well as the pro-inflammatory genes Ccl2 and Il6 were reduced after XBD173 treatment. Light-induced degeneration of the outer retina was nearly fully blocked by XBD173 treatment. We further confirmed these findings in an independent mouse model of focal light damage. Retinas of animals receiving XBD173 therapy displayed significantly more ramified non-reactive microglia and more viable arrestin-positive cone photoreceptors than vehicle controls.Targeting TSPO with XBD173 effectively counter-regulates microgliosis and ameliorates light-induced retinal damage, highlighting a new pharmacological concept for the treatment of retinal degenerations.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB302
    Nombre del producto:
    Anti-Glutamine Synthetase Antibody, clone GS-6

  • Protein phosphatase 2A carboxymethylation and regulatory B subunits differentially regulate mast cell degranulation. 20688157

    Asthma is characterised by antigen-mediated mast cell degranulation resulting in secretion of inflammatory mediators. Protein phosphatase 2A (PP2A) is a serine/threonine protein phosphatase composed of a catalytic (PP2A-C) subunit together with a core scaffold (PP2A-A) subunit and a variable, regulatory (PP2A-B) subunit. Previous studies utilising pharmacological inhibition of protein phosphatases have suggested a positive regulatory role for PP2A in mast cell degranulation. In support of this we find that a high okadaic acid concentration (1μM) inhibits mast cell degranulation. Strikingly, we now show that a low concentration of okadaic acid (0.1μM) has the opposite effect, resulting in enhanced degranulation. Selective downregulation of the PP2A-Cα subunit by short hairpin RNA also enhanced degranulation of RBL-2H3 mast cells, suggesting that the primary role of PP2A is to negatively regulate degranulation. PP2A-B subunits are responsible for substrate specificity, and carboxymethylation of the PP2A-C subunit alters B subunit binding. We show here that carboxymethylation of PP2A-C is dynamically altered during degranulation and inhibition of methylation decreases degranulation. Moreover downregulation of the PP2A-Bα subunit resulted in decreased MK2 phosphorylation and degranulation, whilst downregulation of the PP2A-B'δ subunit enhanced p38 MAPK phosphorylation and degranulation. Taken together these data show that PP2A is both a positive and negative regulator of mast cell degranulation, and this differential role is regulated by carboxymethylation and specific PP2A-B subunit binding.
    Tipo de documento:
    Referencia
    Referencia del producto:
    04-1479
    Nombre del producto:
    Anti-methyl-PP2A Antibody, C subunit, clone 2A10

  • STIL binding to Polo-box 3 of PLK4 regulates centriole duplication. 26188084

    Polo-like kinases (PLK) are eukaryotic regulators of cell cycle progression, mitosis and cytokinesis; PLK4 is a master regulator of centriole duplication. Here, we demonstrate that the SCL/TAL1 interrupting locus (STIL) protein interacts via its coiled-coil region (STIL-CC) with PLK4 in vivo. STIL-CC is the first identified interaction partner of Polo-box 3 (PB3) of PLK4 and also uses a secondary interaction site in the PLK4 L1 region. Structure determination of free PLK4-PB3 and its STIL-CC complex via NMR and crystallography reveals a novel mode of Polo-box-peptide interaction mimicking coiled-coil formation. In vivo analysis of structure-guided STIL mutants reveals distinct binding modes to PLK4-PB3 and L1, as well as interplay of STIL oligomerization with PLK4 binding. We suggest that the STIL-CC/PLK4 interaction mediates PLK4 activation as well as stabilization of centriolar PLK4 and plays a key role in centriole duplication.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MABC544
    Nombre del producto:
    Anti-PLK-4 Antibody, clone 6H5

  • M1 muscarinic receptor activation mediates cell death in M1-HEK293 cells. 24023725

    HEK293 cells have been used extensively to generate stable cell lines to study G protein-coupled receptors, such as muscarinic acetylcholine receptors (mAChRs). The activation of M1 mAChRs in various cell types in vitro has been shown to be protective. To further investigate M1 mAChR-mediated cell survival, we generated stable HEK293 cell-lines expressing the human M1 mAChR. M1 mAChRs were efficiently expressed at the cell surface and efficiently internalised within 1 h by carbachol. Carbachol also induced early signalling cascades similar to previous reports. Thus, ectopically expressed M1 receptors behaved in a similar fashion to the native receptor over short time periods of analysis. However, substantial cell death was observed in HEK293-M1 cells within 24 h after carbachol application. Death was only observed in HEK cells expressing M1 receptors and fully blocked by M1 antagonists. M1 mAChR-stimulation mediated prolonged activation of the MEK-ERK pathway and resulted in prolonged induction of the transcription factor EGR-1 (greater than 24 h). Blockade of ERK signalling with U0126 did not reduce M1 mAChR-mediated cell-death significantly but inhibited the acute induction of EGR-1. We investigated the time-course of cell death using time-lapse microscopy and xCELLigence technology. Both revealed the M1 mAChR cytotoxicity occurs within several hours of M1 activation. The xCELLigence assay also confirmed that the ERK pathway was not involved in cell-death. Interestingly, the MEK blocker did reduce carbachol-mediated cleaved caspase 3 expression in HEK293-M1 cells. The HEK293 cell line is a widely used pharmacological tool for studying G-protein coupled receptors, including mAChRs. Our results highlight the importance of investigating the longer term fate of these cells in short term signalling studies. Identifying how and why activation of the M1 mAChR signals apoptosis in these cells may lead to a better understanding of how mAChRs regulate cell-fate decisions.
    Tipo de documento:
    Referencia
    Referencia del producto:
    06-519
    Nombre del producto:
    Anti-phospho-CREB (Ser133) Antibody

  • The chemokine CXCL12 promotes survival of postmitotic neurons by regulating Rb protein. 18583990

    Postmitotic neurons need to keep their cell cycle under control to survive and maintain a differentiated state. This study aims to test the hypothesis that the chemokine CXCL12 regulates neuronal survival and differentiation by promoting Rb function, as suggested by previous studies showing that CXCL12 protects neurons from apoptosis induced by Rb loss. To this end, the effect of CXCL12 on Rb expression and transcriptional activity and the role of Rb in CXCL12-induced neuronal survival were studied. CXCL12 increases Rb protein and RNA levels in rat cortical neurons. The chemokine also stimulates an exogenous Rb promoter expressed in these neurons and counteracts the inhibition of the Rb promoter induced by E2F1 overexpression. Furthermore CXCL12 stimulates Rb activity as a transcription repressor. The effects of CXCL12 are mediated by its specific receptor CXCR4, and do not require the presence of glia. Finally, shRNA studies show that Rb expression is crucial to the neuroprotective activity of CXCL12 as indicated by NMDA-neurotoxicity assays. These findings suggest that proper CXCR4 stimulation in the mature CNS can prevent impairment of the Rb-E2F pathway and support neuronal survival. This is important to maintain CNS integrity in physiological conditions and prevent neuronal injury and loss typical of many neurodegenerative and neuroinflammatory conditions.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB377
    Nombre del producto:
    Anti-NeuN Antibody, clone A60

  • NKCC1 knockdown decreases neuron production through GABA(A)-regulated neural progenitor proliferation and delays dendrite development. 23015452

    Signaling through GABA(A) receptors controls neural progenitor cell (NPC) development in vitro and is altered in schizophrenic and autistic individuals. However, the in vivo function of GABA(A) signaling on neural stem cell proliferation, and ultimately neurogenesis, remains unknown. To examine GABA(A) function in vivo, we electroporated plasmids encoding short-hairpin (sh) RNA against the Na-K-2Cl cotransporter NKCC1 (shNKCC1) in NPCs of the neonatal subventricular zone in mice to reduce GABA(A)-induced depolarization. Reduced GABA(A) depolarization identified by a loss of GABA(A)-induced calcium responses in most electroporated NPCs led to a 70% decrease in the number of proliferative Ki67(+) NPCs and a 60% reduction in newborn neuron density. Premature loss of GABA(A) depolarization in newborn neurons resulted in truncated dendritic arborization at the time of synaptic integration. However, by 6 weeks the dendritic tree had partially recovered and displayed a small, albeit significant, decrease in dendritic complexity but not total dendritic length. To further examine GABA(A) function on NPCs, we treated animals with a GABA(A) allosteric agonist, pentobarbital. Enhancement of GABA(A) activity in NPCs increased the number of proliferative NPCs by 60%. Combining shNKCC1 and pentobarbital prevented the shNKCC1 and the pentobarbital effects on NPC proliferation, suggesting that these manipulations affected NPCs through GABA(A) receptors. Thus, dysregulation in GABA(A) depolarizing activity delayed dendritic development and reduced NPC proliferation resulting in decreased neuronal density.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB3580
    Nombre del producto:
    Anti-Green Fluorescent Protein Antibody

  • The protective effect of dantrolene on ischemic neuronal cell death is associated with reduced expression of endoplasmic reticulum stress markers. 15921666

    The endoplasmic reticulum (ER) plays an important role in ischemic neuronal cell death. In order to determine the effect of dantrolene, a ryanodine receptor antagonist, on ER stress response and ischemic brain injury, we investigated changes in ER stress-related molecules, that is phosphorylated form of double-stranded RNA-activated protein kinase (PKR)-like ER kinase (p-PERK), phosphorylated form of eukaryotic initiation factor 2alpha (p-eIF2alpha), activating transcription factor-4 (ATF-4), and C/EBP-homologous protein (CHOP), as well as terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in the peri-ischemic area and ischemic core region of rat brain after transient middle cerebral artery occlusion (MCAO). In contrast to the cases treated with vehicle, the infarct volume and TUNEL-positive cells were significantly reduced at 24 h of reperfusion by treatment with dantrolene. The immunoreactivities for p-PERK, p-eIF2alpha, ATF-4, and CHOP were increased at the ischemic peripheral region after MCAO, which were partially inhibited by dantrolene treatment. The present results suggest that dantrolene significantly decreased infarct volume and provided neuroprotective effect on rats after transient MCAO by reducing ER stress-mediated apoptotic signal pathway activation in the ischemic area.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB3402
    Nombre del producto:
    Anti-Glial Fibrillary Acidic Protein Antibody, clone GA5

  • p53 counteracts reprogramming by inhibiting mesenchymal-to-epithelial transition. 22996684

    The process of somatic cell reprogramming is gaining increasing interest as reprogrammed cells are considered to hold a great therapeutic potential. However, with current technologies this process is relatively inefficient. Recent studies reported that inhibition of the p53 tumor suppressor profoundly facilitates reprogramming and attributed this effect to the ability of p53 to restrict proliferation and induce apoptosis. Given that mesenchymal-to-epithelial transition (MET) was recently shown to be necessary for reprogramming of fibroblasts, we investigated whether p53 counteracts reprogramming by affecting MET. We found that p53 restricts MET during the early phases of reprogramming and that this effect is primarily mediated by the ability of p53 to inhibit Klf4-dependent activation of epithelial genes. Moreover, transcriptome analysis revealed a large transcriptional signature enriched with epithelial genes, which is markedly induced by Klf4 exclusively in p53(-/-) cells. We also found that the expression of the epithelial marker E-Cadherin negatively correlates with p53 activity in a variety of mesenchymal cells even before the expression of reprogramming factors. Finally, we demonstrate that the inhibitory effect of p53 on MET is mediated by p21. We conclude that inhibition of the p53-p21 axis predisposes mesenchymal cells to the acquisition of epithelial characteristics and renders them more prone to reprogramming. Our study uncovers a novel mechanism by which p53 restrains reprogramming and highlights the role of p53 in regulating cell plasticity.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB374
    Nombre del producto:
    Anti-Glyceraldehyde-3-Phosphate Dehydrogenase Antibody, clone 6C5