A5015102352- Signaling Pathways in Disease
- Melanoma and MAPK Pathways
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Protein Kinase Regulation and GTPase Signaling
- Immune Response and Inflammation
- Cholinesterase and Neurodegenerative Diseases
- Alzheimer's disease research and treatments
- T-cell and B-cell Immunology
- Quinazolinone synthesis and applications
- Cell Adhesion Molecules Research
- Nerve injury and regeneration
- Synthesis and biological activity
- Microbial Natural Products and Biosynthesis
- Epigenetics and DNA Methylation
- RNA Interference and Gene Delivery
- NF-κB Signaling Pathways
- Neurogenesis and neuroplasticity mechanisms
- Microbial Metabolism and Applications
- Monoclonal and Polyclonal Antibodies Research
- Eicosanoids and Hypertension Pharmacology
- Mechanisms of cancer metastasis
- DNA Repair Mechanisms
Instituto de Salud Carlos III
2010-2021
Unidad Funcional de Investigación de Enfermedades Crónicas
2013-2021
Centro Nacional de Microbiologia
2010-2012
Spanish National Centre for Cardiovascular Research
2005-2008
Universidad Autónoma de Madrid
1990-2006
Consejo Superior de Investigaciones Científicas
2005-2006
Centro de Biología Molecular Severo Ochoa
1994-2006
The Honourable Society of Lincoln's Inn
1999
King's College London
1992-1998
King's College School
1996
Independent of its ability to block translation, anisomycin intrinsically initiates intracellular signals and immediate-early gene induction [L. C. Mahadevan D. R. Edwards, Nature (London) 349:747-749, 1991]. Here, we characterize further action as a potent, selective signalling agonist. In-gel kinase assays show that epidermal growth factor (EGF) transiently activates five kinases: the mitogen-activated protein (MAP) kinases ERK-1 -2, three others, p45, p55, p80. Anisomycin, at inhibitory...
Host injury triggers feedback mechanisms that limit tissue damage. Conventional type 1 dendritic cells (cDC1s) express cell natural killer lectin group receptor-1 (DNGR-1), encoded by the gene Clec9a, which senses damage and favors cross-presentation of dead-cell material to CD8+ T cells. Here we find DNGR-1 additionally reduces host-damaging inflammatory responses induced sterile infectious in mice. deficiency leads exacerbated caerulein-induced necrotizing pancreatitis increased pathology...
Anisomycin, a translational inhibitor secreted by Streptomyces spp., strongly activates the stress-activated mitogen-activated protein (MAP) kinases JNK/SAPK (c-Jun NH2-terminal kinase/stress-activated kinase) and p38/RK in mammalian cells, resulting rapid induction of immediate-early (IE) genes nucleus. Here, we have characterized this response further with respect to homologous heterologous desensitization IE gene stress kinase activation. We show that anisomycin acts exactly like...
Diverse agents, including growth factors and phorbol esters, induce rapid transcriptional activation of a subset immediate-early (IE) genes that include the protooncogenes c-fos c-jun. Among earliest nuclear signaling events concomitant with IE gene is phosphorylation nucleosomal histone H3 in its basically charged N-terminal tail. This highly conserved domain also subject to reversible posttranslational acetylation at specific lysine residues, process implicated regulation. We show here...
Brain CD11c+ cells share features with microglia and dendritic (DCs). Sterile inflammation increases brain cells, but their phenotype, origin, functions remain largely unknown. We report that, after cerebral ischemia, attract DCs to the inflamed brain, astroglia produce Flt3 ligand, supporting development expansion of cells. in are a complex population derived from proliferating infiltrating DCs, including major subset OX40L+ conventional cDC2, also cDC1, plasmacytoid, monocyte-derived DCs....
Abstract Background An increase in intracellular calcium concentration [Ca 2+ ] i is one of the first events to take place after brain ischemia. A key -regulated signaling molecule phosphatase calcineurin (CN), which plays important roles modulation inflammatory cascades. Here, we have analyzed role endogenous regulator CN 1 (Rcan1) response experimental ischemic stroke induced by middle cerebral artery occlusion. Methods Animals were subjected focal ischemia with reperfusion. To assess...
The study of factors that regulate the survival, proliferation, and differentiation neural precursor cells (NPCs) is essential to understand development as well brain regeneration. Nuclear Factor Activated T Cells (NFAT) a family transcription can affect these processes besides playing key roles during development, such stimulating axonal growth in neurons, maturation immune system cells, heart valve formation, skeletal muscle bone. Interestingly, NFAT signaling also promote cell adults,...
The nuclear factor of activated T cells (NFAT) family transcription factors regulates the cytokine genes and other involved in regulation function immune system. NFAT activity is regulated by phosphatase calcineurin, which binds dephosphorylates N-terminal regulatory domain, a critical step required for translocation transcriptional activity. Here we show that mitogen-activated protein kinase (MAPK) JNK activates NFATc2-dependent transcription. Mass spectrometry revealed phosphorylates at...
Abstract The calcineurin/nuclear factor of activated T cells (NFAT) signaling pathway mediates important cell responses to calcium, but its activity and function in astrocytes have remained unclear. We show that primary cortical astrocyte cultures express the regulatory catalytic subunits phosphatase calcineurin as well calcium‐regulated NFAT family members (NFATc1, c2, c3, c4). NFATs are by calcium‐mobilizing agents astrocytes, this activation is blocked inhibitor cyclosporine A. Microarray...
The role and different origin of brain myeloid cells in the is central to understanding how nervous system (CNS) responds injury. C-type lectin receptor family 9, member A (DNGR-1/CLEC9A) a marker specific DC subsets that share functional similarities, such as CD8α+DCs lymphoid tissues CD103+CD11blowDCs peripheral tissues. Here, we analyzed presence DNGR-1 DCs present mouse (bDCs). Dngr-1/Clec9a mRNA expressed mainly meningeal membranes choroid plexus (m/Ch), its expression enhanced by...
ABSTRACT The effects of EGF, TPA, UV radiation, okadaic acid and anisomycin on ERK JNK/SAPK MAP kinase cascades have been compared with their ability to elicit histone H3/HMG-14 phosphorylation induce c-fos c-jun in C3H 10TG cells. EGF radiation activate both ERKs JNK/SAPKs but markedly different extents; activates more strongly than JNK/SAPKs, whereas much ERKs. Anisomycin not ERKs, conversely, TPA JNK/SAPKs. Nevertheless, all these agents ribosomal pre-ribosomal S6, H3 HMG-14, the...
In this study we showed that the transcriptional regulation of Down syndrome critical region isoform 4 (DSCR1.4) is mediated by calcineurin/nuclear factor activated T cells (NFAT) pathway in neural cells. Stimuli elicit an increase intracellular concentrations calcium, such as membrane depolarization, induced de novo transcription DSCR1.4, with mRNA expression peaking after h and then declining. Action via physiologically relevant L-type calcium channel was confirmed blockade nifedipine...
Abstract Astrocytes react to brain injury triggering neuroinflammatory processes that determine the degree of neuronal damage. However, signaling events associated astrocyte activation remain largely undefined. The nuclear factor activated T‐cells (NFAT) is a transcription family implicated in immune cells. We previously characterized expression NFAT isoforms cultured astrocytes, and response mechanical lesion. Here we analyze NFATc3 two mouse models inflammatory damage: hippocampal...
Independent of its ability to block translation, anisomycin intrinsically initiates intracellular signals and immediate-early gene induction [L. C. Mahadevan D. R. Edwards, Nature (London) 349:747-749, 1991]. Here, we characterize further action as a potent, selective signalling agonist. In-gel kinase assays show that epidermal growth factor (EGF) transiently activates five kinases: the mitogen-activated protein (MAP) kinases ERK-1 -2, three others, p45, p55, p80. Anisomycin, at inhibitory...
Abstract: Tumor necrosis factor‐a (TNF‐α), interferon‐γ (IFN‐7), and interleukin‐6 (IL‐6), but not TNF‐β, can induce the in vitro differentiation of neuroblastoma cell line N103 a dose‐dependent manner. Differentiation was accompanied by arrest growth neurite formation. The induction TNF‐α IFN‐γ be specifically inhibited nitric oxide (NO) synthase inhibitor, l ‐N G ‐monomethylarginine. In contrast, cells IL‐6 affected These results indicate that IFN‐γ, IL‐6, via NO. This is confirmed finding...
Increase in intracellular calcium ([Ca 2+ ] i ) is a key mediator of astrocyte signaling, important for activation the calcineurin (CN)/nuclear factor activated T cells (NFAT) pathway, central inflammatory events. We analyzed expression matrix metalloproteinase 3 ( Mmp3 response to increases [Ca and role CN/NFAT pathway this regulation. Astrocyte was induced by overexpression constitutively active form NFATc3, whereas other MMPs tissue inhibitor metalloproteinases (TIMP) were unaffected....
Abstract Calcium/Calcineurin/Nuclear Factor of Activated T cells (Ca/CN/NFAT) signalling pathway is the main calcium (Ca 2+ ) dependent involved in homeostasis brain tissue. Here, we study presence NFATc members human glioma by using U251 and a collection primary glioblastoma (hGB) cell lines. We show that NFATc3 member predominant member. Furthermore, constitutive active mutant shRNA lentiviral vectors to achieve specific silencing this member, describe cytokines molecules regulated which...