Examinando por Autor "Fuentealba, Jorge"

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    Copper-uptake is critical for the down regulation of synapsin and dynamin induced by neocuproine: Modulation of synaptic activity in hippocampal neurons
    (Frontiers Research Foundation, 2014) Castro, Patricio A.; Ramirez, Alejandra; Sepúlveda, Fernando J.; Peters, Christian; Fierro, Humberto; Waldron, Javier; Luza, Sandra; Fuentealba, Jorge; Muñoz, Francisco J.; De Ferrari, Giancarlo V.; Bush, Ashley I.; Aguayo, Luis G.; Opazo, Carlos
    Extracellular and intracellular copper and zinc regulate synaptic activity and plasticity, which may impact brain functionality and human behavior. We have found that a metal coordinating molecule, Neocuproine, transiently increases free intracellular copper and zinc levels (i.e., min) in hippocampal neurons as monitored by Phen Green and FluoZin 3 fluorescence, respectively. The changes in free intracellular zinc induced by Neocuproine were abolished by the presence of a non-permeant copper chelator, Bathocuproine (BC), indicating that copper influx is needed for the action of Neocuproine on intracellular Zn levels. Moreover, Neocuproine decreased the mRNA levels of Synapsin and Dynamin, and did not affect the expression of Bassoon, tubulin or superoxide dismutase (SOD). Western blot analysis showed that protein levels of synapsin and dynamin were also down regulated in the presence of Neocuproine and that these changes were accompanied by a decrease in calcium transients and neuronal activity. Furthermore, Neocuproine decreased the number of active neurons, effect that was blocked by the presence of BC, indicating that copper influx is needed for the action of Neocuproine. We finally show that Neocuproine blocks the epileptiform-like activity induced by bicuculline in hippocampal neurons. Collectively, our data indicates that presynaptic protein configuration and function of primary hippocampal neurons is sensitive to transient changes in transition metal homeostasis. Therefore, small molecules able to coordinate transition metals and penetrate the blood-brain barrier might modify neurotransmission at the Central Nervous System (CNS). This might be useful to establish therapeutic approaches to control the neuronal hyperexcitabiltity observed in brain conditions that are associated to copper dyshomeotasis such as Alzheimer’s and Menkes diseases. Our work also opens a new avenue to find novel and effective antiepilepsy drugs based in metal coordinating molecules.
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    Ítem
    Reversal of ethanol-induced intoxication by a novel modulator of Gβγ protein potentiation of the glycine receptor
    (American Society for Biochemistry and Molecular Biology Inc., 2016-09) San Martin, Loreto; Cerda, Fabian; Jin, Chunyang; Jimenez, Veronica; Yevenes, Gonzalo E.; Hernandez, Tania; Nova, Daniela; Fuentealba, Jorge; Aguayo, Luis G.; Guzman, Leonardo
    The acute intoxicating effects of ethanol in the central nervous system result from the modulation of several molecular targets. It is widely accepted that ethanol enhances the activity of the glycine receptor (GlyR), thus enhancing inhibitory neurotransmission, leading to motor effects, sedation, and respiratory depression. We previously reported that small peptides interfered with the binding of Gβγ to the GlyR and consequently inhibited the ethanol-induced potentiation of the receptor. Now, using virtual screening, we identified a subset of small molecules capable of interacting with the binding site of Gβγ. One of these compounds, M554, inhibited the ethanol potentiation of the GlyR in both evoked currents and synaptic transmission in vitro. When this compound was tested in vivo in mice treated with ethanol (1–3.5 g/kg), it was found to induce a faster recovery of motor incoordination in rotarod experiments and a shorter sedative effect in loss of righting reflex assays. This study describes a novel molecule that might be relevant for the design of useful therapeutic compounds in the treatment of acute alcohol intoxication.
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    VALORACIÓN ECONOMICA DE LA EMPRESA CEMEX MEXICO S.A. Y FILIALES
    (Universidad Andrés Bello, 2014) Fuentealba, Jorge; Orellana Yáñez, Oscar; Jerez Frank, Valeria.; Facultad de Economía y Negocios; Escuela de Ingeniería en Administración de Empresas
    El presente seminario de título tuvo como objetivo general la realización de una valoración económica CEMEX México, S.A. de C.V, CEMEX Corp. y CEMEX Asia Holding Ltd. a través de los métodos de fundamentos y de múltiplos comparables. Lo anterior, se efectuó considerando información de los estados financieros y memorias de la empresa y filiales. Para realización de proyecciones de los flujos de caja libre, se utilizaron datos sobre las expectativas de crecimiento que presenta CEMEX y Filiales, lo que permitió realizar los descuentos a una tasa WACC estimada, con el fin de obtener como resultado el valor económico de éstas.