<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Baxter-Parker G</dc:creator>
  <dc:creator>Prebble HM</dc:creator>
  <dc:creator>Cross S</dc:creator>
  <dc:creator>Steyn N</dc:creator>
  <dc:creator>Shchepetkina A</dc:creator>
  <dc:creator>Hock BD</dc:creator>
  <dc:creator>Cousins A</dc:creator>
  <dc:creator>Gieseg SP</dc:creator>
  <dc:date>2020</dc:date>
  <dc:description xmlns:ns0="xml" ns0:lang="en">Clinical measurement of neopterin has been extensively used as a marker of inflammation but the in vivo mechanism generating neopterin is poorly understood. Neopterin is described as the oxidation product of 7,8-dihydroneopterin, a potent antioxidant generated by monocyte/macrophages in response to interferon-γ. While peroxyl and hydroxyl scavenging generates dihydroxanthopterin, hypochlorite efficiently oxidises 7,8-dihydroneopterin into neopterin, but this reaction alone does not explain the high levels of neopterin seen in clinical data. Here, we examine whether superoxide scavenging by 7,8-dihydroneopterin generates neopterin. U937 cells incubated with oxLDL showed a time dependent increase superoxide and 7,8-dihydroneopterin oxidation to neopterin. Neopterin generation in oxLDL or phorbol ester treated U937 cells or human monocytes was inhibited by apocynin and PEG-SOD. Addition of the myeloperoxidase inhibitor 4-aminobenzoic acid hydrazide (ABAH) had no effect of the superoxide generation or neopterin formation. 7,8-Dihydroneopterin reacted with superoxide/hydroxy radical mixtures generated by X-ray radiolysis to give neopterin. Formation of neopterin by superoxide derived from the xanthine/xanthine oxidase system was inhibited by superoxide dismutase. Neopterin formation was inhibited by apocynin in phorbol ester treated human carotid plaque rings in tissue culture. These results indicate that 7,8-dihydroneopterin scavenges superoxide and is subsequently oxidised into neopterin in cellular and cell-free experimental systems.</dc:description>
  <dc:identifier>https://sonar.ch/global/documents/105427</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>info:eu-repo/semantics/altIdentifier/doi/10.1016/j.freeradbiomed.2020.03.002</dc:relation>
  <dc:relation>info:eu-repo/semantics/altIdentifier/pmid/32145301</dc:relation>
  <dc:source>Free radical biology &amp; medicine. - 2020</dc:source>
  <dc:subject xmlns:ns1="xml" ns1:lang="en">7,8-Dihydroneopterin</dc:subject>
  <dc:subject xmlns:ns2="xml" ns2:lang="en">Antioxidant</dc:subject>
  <dc:subject xmlns:ns3="xml" ns3:lang="en">Atherosclerotic plaque</dc:subject>
  <dc:subject xmlns:ns4="xml" ns4:lang="en">Macrophages</dc:subject>
  <dc:subject xmlns:ns5="xml" ns5:lang="en">Neopterin</dc:subject>
  <dc:subject xmlns:ns6="xml" ns6:lang="en">Radiolysis</dc:subject>
  <dc:subject xmlns:ns7="xml" ns7:lang="en">Superoxide</dc:subject>
  <dc:title xmlns:ns8="xml" ns8:lang="en">Neopterin formation through radical scavenging of superoxide by the macrophage synthesised antioxidant 7,8-dihydroneopterin.</dc:title>
  <dc:type>http://purl.org/coar/resource_type/c_6501</dc:type>
</oai_dc:dc>