94 research outputs found

    Calreticulin Enhances the Transcriptional Activity of Thyroid Transcription Factor-1 by Binding to Its Homeodomain

    Get PDF
    Transcription factors are often regulated by associated protein cofactors that are able to modify their activity by several different mechanisms. In this study we show that calreticulin, a Ca2+-binding protein with chaperone activity, binds to thyroid transcription factor-1 (TTF-1), a homeodomain-containing protein implicated in the differentiation of lung and thyroid. The interaction between calreticulin and TTF-1 appears to have functional significance because it results in increased transcriptional stimulation of TTF-1-dependent promoters. Calreticulin binds to the TTF-1 homeodomain and promotes its folding, suggesting that the mechanism involved in stimulation of transcriptional activity is an increase of the steady-state concentration of active TTF-1 protein in the cell. We also demonstrate that calreticulin mRNA levels in thyroid cells are under strict control by the thyroid-stimulating hormone, thus implicating calreticulin in the modulation of thyroid gene expression by thyroid-stimulating hormone

    Bioactive Phenolic Compounds in the Modulation of Central and Peripheral Nervous System Cancers: Facts and Misdeeds.

    Get PDF
    Efficacious therapies are not available for the cure of both gliomas and glioneuronal tumors, which represent the most numerous and heterogeneous primary cancers of the central nervous system (CNS), and for neoplasms of the peripheral nervous system (PNS), which can be divided into benign tumors, mainly represented by schwannomas and neurofibromas, and malignant tumors of the peripheral nerve sheath (MPNST). Increased cellular oxidative stress and other metabolic aspects have been reported as potential etiologies in the nervous system tumors. Thus polyphenols have been tested as effective natural compounds likely useful for the prevention and therapy of this group of neoplasms, because of their antioxidant and anti-inflammatory activity. However, polyphenols show poor intestinal absorption due to individual intestinal microbiota content, poor bioavailability, and difficulty in passing the blood–brain barrier (BBB). Recently, polymeric nanoparticle-based polyphenol delivery improved their gastrointestinal absorption, their bioavailability, and entry into defined target organs. Herein, we summarize recent findings about the primary polyphenols employed for nervous system tumor prevention and treatment. We describe the limitations of their application in clinical practice and the new strategies aimed at enhancing their bioavailability and targeted delivery. © 2020 by the authors

    The Complexity of Sporadic Alzheimer's Disease Pathogenesis: The Role of RAGE as Therapeutic Target to Promote Neuroprotection by Inhibiting Neurovascular Dysfunction

    Get PDF
    Alzheimer's disease (AD) is the most common cause of dementia. Amyloid plaques and neurofibrillary tangles are prominent pathological features of AD. Aging and age-dependent oxidative stress are the major nongenetic risk factors for AD. The beta-amyloid peptide (Aβ), the major component of plaques, and advanced glycation end products (AGEs) are key activators of plaque-associated cellular dysfunction. Aβ and AGEs bind to the receptor for AGEs (RAGE), which transmits the signal from RAGE via redox-sensitive pathways to nuclear factor kappa-B (NF-κB). RAGE-mediated signaling is an important contributor to neurodegeneration in AD. We will summarize the current knowledge and ongoing studies on RAGE function in AD. We will also present evidence for a novel pathway induced by RAGE in AD, which leads to the expression of thioredoxin interacting protein (TXNIP), providing further evidence that pharmacological inhibition of RAGE will promote neuroprotection by blocking neurovascular dysfunction in AD

    Is Drp1 a link between mitochondrial dysfunction and inflammation in Alzheimer's disease?

    Get PDF
    Recent advances highlight that inflammation is critical to Alzheimer Disease (AD) pathogenesis. Indeed, several diseases characterized by inflammation are considered risk factors for AD, such as type 2 diabetes, obesity, hypertension, and traumatic brain injury. Moreover, allelic variations in genes involved in the inflammatory cascade are risk factors for AD. AD is also characterized by mitochondrial dysfunction, which affects the energy homeostasis of the brain. The role of mitochondrial dysfunction has been characterized mostly in neuronal cells. However, recent data are demonstrating that mitochondrial dysfunction occurs also in inflammatory cells, promoting inflammation and the secretion of pro-inflammatory cytokines, which in turn induce neurodegeneration. In this review, we summarize the recent finding supporting the hypothesis of the inflammatory-amyloid cascade in AD. Moreover, we describe the recent data that demonstrate the link between altered mitochondrial dysfunction and the inflammatory cascade. We focus in summarizing the role of Drp1, which is involved in mitochondrial fission, showing that altered Drp1 activation affects the mitochondrial homeostasis and leads to the activation of the NLRP3 inflammasome, promoting the inflammatory cascade, which in turn aggravates Amyloid beta (Ab) deposition and tau-induced neurodegeneration, showing the relevance of this pro-inflammatory pathway as an early event in AD

    GAP-43 slows down cell cycle progression via sequences in its 3′UTR

    Get PDF
    Growth-associated protein 43 (GAP-43) is a neuronal phosphoprotein associated with initial axonal outgrowth and synaptic remodeling and recent work also suggests its involvement in cell cycle control. The complex expression of GAP-43 features transcriptional and posttranscriptional components. However, in some conditions, GAP-43 gene expression is controlled primarily by the interaction of stabilizing or destabilizing RNA-binding proteins (RBPs) with adenine and uridine (AU)-rich instability elements (AREs) in its 3′UTR. Like GAP-43, many proteins involved in cell proliferation are encoded by ARE-containing mRNAs, some of which codify cell-cycle-regulating proteins including cyclin D1. Considering that GAP-43 and cyclin D1 mRNA stabilization may depend on similar RBPs, this study evaluated the participation of GAP-43 in cell cycle control and its underlying mechanisms, particularly the possible role of its 3′UTR, using GAP-43-transfected NIH-3T3 fibroblasts. Our results show an arrest in cell cycle progression in the G0/G1 phase. This arrest may be mediated by the competition of GAP-43 3′UTR with cyclin D1 3′UTR for the binding of Hu proteins such as HuR, which may lead to a decrease in cyclin D1 expression. These results might lead to therapeutic applications involving the use of sequences in the B region of GAP-43 3′UTR to slow down cell cycle progression.Fil: de Moliner, Karina Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Wolfson, Manuel Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Perrone Bizzozero, Nora. University of New Mexico; Estados UnidosFil: Adamo, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentin

    Organizaciones escolares flexibles: las nuevas formas de adaptación

    Get PDF
    La impronta neoliberal, con la Reforma del Estado que cuestiona al aparato burocrático por lento, ineficaz y costoso, se introdujo en las escuelas, con las reformas educativas que se extendieron en América Latina en los últimos veinte años. El imperativo de renovación vino de la mano de las críticas a la burocracia estatal y a los modelos de organización rígida y dependiente que caracterizaron el origen y desarrollo de los sistemas educativos, colapsados en la post modernidad y acusados por su baja productividad y el deterioro de la calidad de sus servicios. Desde el discurso y los cuerpos normativos se impulsó en las escuelas un proceso caracterizado – entre otras cosas – por la fuerte imposición de nuevos significados que afectaron las prácticas y la visión de los docentes sobre el “modo de hacer escuela”. Este trabajo focaliza la mirada en torno a la flexibilidad que se requiere hoy a las escuelas, a la par que se las dota de autonomía para que diseñen e implementen acciones innovadoras con estrategias participativas democratizadoras, lo que les permitirá responder a las exigencias actuales mejorando así la calidad de sus servicios.Facultad de Humanidades y Ciencias de la Educació

    Immune system effectors as biomarkers of prognosis after acute burns in a case-control study

    Get PDF
    Burns are a global health problem due to frequent complications, which lead to systemic inflammation, acute respiratory distresssyndrome, multiorgan dysfunction, and death. Following the initial injury, it has been demonstrated that the immune system plays akey role in early inflammation, tissue regeneration, and the response against pathogens. In this study, the performance of laboratorydeterminations as biomarkers of prognosis in acute burned patients was evaluated in a retrospective case-control protocol.Laboratory determinations were immunoglobulin G (IgG), immunoglobulin M (IgM), C-reactive protein (CRP), complement C4protein (C4), total serum protein (TP), albumin, prealbumin, cholesterol (CHOL), pseudocholinesterase activity (CHE), andtransferrin. Patients in the deceased group (DG) showed lower initial IgG levels (p < 0.05) than patients in the survivor group (SG),with a negative predictive value (NPV) of 0.86, and this difference persisted during the hospitalization period. Furthermore, DGpatients showed a decrease in CHOL and CHE during the hospitalization period (NPV of 0.86), a tendency that was not observed forthe SG. Albumin, TP, C4, and transferrin showed lower initial values in DG than the SG, with a strong correlation with the totalburned surface area (TBSA). These results indicate that IgG, CHOL, and CHE measurement might provide useful information formedical intervention independently of the TBSA and suggest that the measurement of TBSA-linked parameters might help toestimate the severity of burns more objectively. In this paper, the causes and implications of the alteration of effector molecules ofthe immune system are discussed.Fil: Ferrari, Alejandro. Instituto Nacional del Agua. Gerencia de Programas y Proyectos. Centro de la Region Semiarida.; Argentina. Hospital Municipal de Quemados Dr. Arturo Umberto Illia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Di Croce, Lorena. Hospital Municipal de Quemados Dr. Arturo Umberto Illia; ArgentinaFil: Saavedra, Sabrina. Hospital Municipal de Quemados Dr. Arturo Umberto Illia; ArgentinaFil: Hartwig, Marisel. Hospital Municipal de Quemados Dr. Arturo Umberto Illia; ArgentinaFil: Perrone, Omar. Hospital Municipal de Quemados Dr. Arturo Umberto Illia; ArgentinaFil: Guzmán, María Alejandra. Hospital Municipal de Quemados Dr. Arturo Umberto Illia; Argentin

    Activation of APE1/Ref-1 is dependent on reactive oxygen species generated after purinergic receptor stimulation by ATP

    Get PDF
    Apurinic apyrimidinic endonuclease redox effector factor-1 (APE1/Ref-1) is involved both in the base excision repair (BER) of DNA lesions and in the eukaryotic transcriptional regulation. APE1/Ref-1 is regulated at both the transcriptional and post-translational levels, through control of subcellular localization and post-translational modification. In response to stress conditions, several cell types release ATP, which exerts stimulatory effects on eukaryotic cells via the purinergic receptors (P2) family. By using western blot and immunofluorescence analysis on a human tumour thyroid cell line (ARO), we demonstrate that purinergic stimulation by extracellular ATP induces quick cytoplasm to nucleus translocation of the protein at early times and its neosynthesis at later times. Continuous purinergic triggering by extracellular ATP released by ARO cells is responsible for the control of APE1/Ref-1 intracellular level. Interference with intracellular pathways activated by P2 triggering demonstrates that Ca(2+) mobilization and intracellular reactive oxygen species (ROS) production are responsible for APE1/Ref-1 translocation. The APE1/Ref-1 activities on activator protein-1 (AP-1) DNA binding and DNA repair perfectly match its nuclear enrichment upon ATP stimulation. The biological relevance of our data is reinforced by the observation that APE1/Ref-1 stimulation by ATP protects ARO cells by H(2)O(2)-induced cell death. Our data provide new insights into the complex mechanisms regulating APE1/Ref-1 functions

    La reproducción en el campo educativo : Aportes para una lectura sociológica del texto escolar

    Get PDF
    En este trabajo interesa reflexionar sobre la función reproductora de la escuela y centrar la mirada en el “Cómo”, analizando los medios y/o prácticas de que se vale para llevarla a cabo. El abordaje se realiza teniendo en cuenta la tecnología en su doble acepción: en la organización de la escuela (aspecto estático) y en el funcionamiento de la misma (aspectos dinámicos), para rescatar la lógica que impregna los procesos de enseñanza y aprendizaje y el papel del docente en ellos, como así también los soportes o recursos de que dispone. Interesa particularmente el libro de texto – o manual - para analizar el discurso que por ellos circula y el uso que los docentes hacen de él.Jornadas realizadas junto con el I Encuentro Latinoamericano de Metodología de las Ciencias Sociales.Facultad de Humanidades y Ciencias de la Educació

    Plasma-activated Ringer's Lactate Solution Displays a Selective Cytotoxic Effect on Ovarian Cancer Cells

    Get PDF
    Epithelial Ovarian Cancer (EOC) is one of the leading causes of cancer-related deaths among women and is characterized by the diffusion of nodules or plaques from the ovary to the peritoneal surfaces. Conventional therapeutic options cannot eradicate the disease and show low efficacy against resistant tumor subclones. The treatment of liquids via cold atmospheric pressure plasma enables the production of plasma-activated liquids (PALs) containing reactive oxygen and nitrogen species (RONS) with selective anticancer activity. Thus, the delivery of RONS to cancer tissues by intraperitoneal washing with PALs might be an innovative strategy for the treatment of EOC. In this work, plasma-activated Ringer's Lactate solution (PA-RL) was produced by exposing a liquid substrate to a multiwire plasma source. Subsequently, PA-RL dilutions are used for the treatment of EOC, non-cancer and fibroblast cell lines, revealing a selectivity of PA-RL, which induces a significantly higher cytotoxic effect in EOC with respect to non-cancer cells
    corecore