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Sulforaphane Inhibits Lipopolysaccharide-Induced Inflammation, Cytotoxicity, Oxidative Stress, and miR-155 Expression and Switches to Mox Phenotype through Activating Extracellular Signal-Regulated Kinase 1/2-Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway in Murine Microglial Cells

Eren, Erden; Tufekci, Kemal Ugur; Isci, Kamer Burak; Tastan, Bora; Genc, Kursad; Genc, Sermin


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  <identifier identifierType="URL">https://aperta.ulakbim.gov.tr/record/36753</identifier>
  <creators>
    <creator>
      <creatorName>Eren, Erden</creatorName>
      <givenName>Erden</givenName>
      <familyName>Eren</familyName>
    </creator>
    <creator>
      <creatorName>Tufekci, Kemal Ugur</creatorName>
      <givenName>Kemal Ugur</givenName>
      <familyName>Tufekci</familyName>
    </creator>
    <creator>
      <creatorName>Isci, Kamer Burak</creatorName>
      <givenName>Kamer Burak</givenName>
      <familyName>Isci</familyName>
    </creator>
    <creator>
      <creatorName>Tastan, Bora</creatorName>
      <givenName>Bora</givenName>
      <familyName>Tastan</familyName>
    </creator>
    <creator>
      <creatorName>Genc, Kursad</creatorName>
      <givenName>Kursad</givenName>
      <familyName>Genc</familyName>
      <affiliation>Dokuz Eylul Univ, Hlth Sci Inst, Dept Neurosci, Izmir, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Genc, Sermin</creatorName>
      <givenName>Sermin</givenName>
      <familyName>Genc</familyName>
    </creator>
  </creators>
  <titles>
    <title>Sulforaphane Inhibits Lipopolysaccharide-Induced Inflammation, Cytotoxicity, Oxidative Stress, And Mir-155 Expression And Switches To Mox Phenotype Through Activating Extracellular Signal-Regulated Kinase 1/2-Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway In Murine Microglial Cells</title>
  </titles>
  <publisher>Aperta</publisher>
  <publicationYear>2018</publicationYear>
  <dates>
    <date dateType="Issued">2018-01-01</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://aperta.ulakbim.gov.tr/record/36753</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.3389/fimmu.2018.00036</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="http://www.opendefinition.org/licenses/cc-by">Creative Commons Attribution</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">Sulforaphane (SFN) is a natural product with cytoprotective, anti-inflammatory, and antioxidant effects. In this study, we evaluated the mechanisms of its effects on lipopolysaccharide (LPS)-induced cell death, inflammation, oxidative stress, and polarization in murine microglia. We found that SFN protects N9 microglial cells upon LPS-induced cell death and suppresses LPS-induced levels of secreted pro-inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6. SFN is also a potent inducer of redox sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), which is responsible for the transcription of antioxidant, cytoprotective, and anti-inflammatory genes. SFN induced translocation of Nrf2 to the nucleus via extracellular signal-regulated kinase 1/2 (ERK1/2) pathway activation. siRNA-mediated knockdown study showed that the effects of SFN on LPS-induced reactive oxygen species, reactive nitrogen species, and pro-inflammatory cytokine production and cell death are partly Nrf2 dependent. Mox phenotype is a novel microglial phenotype that has roles in oxidative stress responses. Our results suggested that SFN induced the Mox phenotype in murine microglia through Nrf2 pathway. SFN also alleviated LPS-induced expression of inflammatory microRNA, miR-155. Finally, SFN inhibits microglia-mediated neurotoxicity as demonstrated by conditioned medium and co-culture experiments. In conclusion, SFN exerts protective effects on microglia and modulates the microglial activation state.</description>
  </descriptions>
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