Taurine chloramine modulates nitric oxide production by activated BV-2 cells.
Item
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Title
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Taurine chloramine modulates nitric oxide production by activated BV-2 cells.
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Identifier
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AAI3213135
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identifier
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3213135
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Creator
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Serban, Valeria.
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Contributor
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Adviser: Michael R. Quinn
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Date
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2006
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Neuroscience
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Abstract
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Taurine (2-aminoethanesulfonic acid) is a beta-amino acid present in animal cells at high intracellular concentrations, but not incorporated into proteins. Taurine protects against inflammation-induced tissue damage. Although the mechanism through which taurine provides protection is uncertain, the formation of taurine monochloramine (Tau-Cl) and its subsequent actions appears to be important.;Tau-Cl formation requires the presence of a halide-dependent myeloperoxidase (MPO) system, which is associated primarily with neutrophils. Taurine reacts with hypochlorous acid (HOCI), an aggressive oxidant, to form taurine chloramine (Tau-Cl), a more stable and selective oxidant that also functions as a modulator of the inflammatory response by inhibiting the production of inflammatory mediators.;In this work we focused on nitric oxide (NO), a short-lived gas molecule, with roles in neural degeneration, demyelination and inflammatory response. NO is produced from L-arginine by the catalytic enzyme nitric oxide synthase (NOS). Microglia and astrocytes are the major immunoresponsive cells in the CNS and when activated express inducible NOS (iNOS). Although there are reports describing the inhibitory effects of Tau-Cl on inflammatory mediators production by activated astrocytes, Tau-Cl modulation of activated microglia has not yet been examined.;The primary goal of the present investigation was to determine the effects of TauCl on NO production by activated BV-2 cells and the molecular mechanisms through which Tau-Cl exerts its effect. Cultures of BV-2 cells were activated with lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), and a combination of both LPS and IFN-gamma. Tau-Cl dose-dependently inhibited NO production by activated BV-2 cells, regardless of the stimulator. Nitric oxide inhibition was parallel with iNOS protein downregulation by the Tau-Cl treatment. The BV-2 cells responded independently to LPS and IFN-gamma, allowing separate investigation of the two signaling pathways: NF-kappaB for LPS and JAK/Stat for IFN-gamma. In addition, Tau-Cl modulated iNOS gene transcription by inhibiting the activity of the transcription factors NF-kappaB and Stat-1.;This study has clinical relevance, suggesting the role of taurine as a potential therapeutic agent. Intervention with pharmacological doses of taurine in the acute phase of inflammation could, via taurine chloramine formation, downregulate the CNS inflammatory response.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
