Pubmed-entry ::= {
  pmid 21922517,
  medent {
    em std {
      year 2011,
      month 11,
      day 17
    },
    cit {
      title {
        name "Hypoxia-induced upregulation of pigment epithelium-derived
 factor by retinal glial (Muller) cells."
      },
      authors {
        names ml {
          "Yang XM",
          "Yafai Y",
          "Wiedemann P",
          "Kuhrt H",
          "Wang YS",
          "Reichenbach A",
          "Eichler W"
        },
        affil str "Department of Ophthalmology and Eye Hospital, University of
 Leipzig, Leipzig, Germany."
      },
      from journal {
        title {
          iso-jta "J. Neurosci. Res.",
          ml-jta "J Neurosci Res",
          issn "1097-4547",
          name "Journal of neuroscience research"
        },
        imp {
          date std {
            year 2012,
            month 1
          },
          volume "90",
          issue "1",
          pages "257-266",
          language "eng",
          pubstatus ppublish,
          history {
            {
              pubstatus received,
              date std {
                year 2010,
                month 11,
                day 8
              }
            },
            {
              pubstatus revised,
              date std {
                year 2011,
                month 6,
                day 6
              }
            },
            {
              pubstatus accepted,
              date std {
                year 2011,
                month 6,
                day 6
              }
            },
            {
              pubstatus aheadofprint,
              date std {
                year 2011,
                month 9,
                day 15
              }
            },
            {
              pubstatus other,
              date std {
                year 2011,
                month 9,
                day 17,
                hour 6,
                minute 0
              }
            },
            {
              pubstatus pubmed,
              date std {
                year 2011,
                month 9,
                day 17,
                hour 6,
                minute 0
              }
            },
            {
              pubstatus medline,
              date std {
                year 2012,
                month 3,
                day 14,
                hour 6,
                minute 0
              }
            }
          }
        }
      },
      ids {
        doi "10.1002/jnr.22732",
        pubmed 21922517,
        other {
          db "ELocationID doi",
          tag str "10.1002/jnr.22732"
        }
      }
    },
    abstract "Neuronal degeneration and aberrant neovascularization are common
 problems of ischemic retinopathies. Pigment epithelium-derived factor (PEDF),
 a neuroprotective protein and an inhibitor of angiogenesis, is produced by
 retinal glial (Muller) cells and can counterbalance elevated levels of
 vascular endothelial growth factor (VEGF), the expression of which is
 regulated primarily by hypoxia-inducible factor (HIF)-1. In an approach to
 mimic transient ischemia in vitro, primary Muller cells were cultured under
 transient and strong hypoxia (0.2% O(2) ), followed by reoxygenation at 2.5%
 O(2) , and molecular mechanisms that might contribute to changes in the
 intraretinal PEDF level were determined. Hypoxic conditions caused an
 increasing expression of HIF-1alpha and led to upregulation of both PEDF and
 VEGF. Treatment of the cells with synthetic HIF-1alpha blockers or
 neutralization of VEGF binding to VEGF receptors (VEGFR-1 and-2) suppressed
 hypoxia-induced PEDF upregulation. Furthermore, the presence of CoCl(2) (a
 hypoxia mimetic) induced an accumulation of elevated HIF-1alpha protein in
 the nucleus and an upregulation of PEDF expression in Muller cells.
 Increasing PEDF expression was attenuated when HIF-1alpha levels were
 suppressed using HIF-1alpha small interfering RNA (siRNA). On the other hand,
 siRNA-mediated depletion of PEDF facilitated HIF-1alpha upregulation caused
 by CoCl(2) and resulted in increasing VEGF mRNA and protein levels. These
 results demonstrate that VEGF and PEDF may be unidirectionally regulated in
 hypoxia through HIF-1alpha activation, with upregulation of PEDF, which may
 occur in a VEGF-dependent manner. However, endogenously produced PEDF seems
 to be an inherent control element of HIF-1alpha expression in Muller cells,
 indicating an important feedback mechanism for limiting upregulation of VEGF.",
    mesh {
      {
        term "Animals"
      },
      {
        term "Animals, Newborn"
      },
      {
        term "Anoxia",
        qual {
          {
            mp TRUE,
            subh "metabolism"
          }
        }
      },
      {
        term "Cells, Cultured"
      },
      {
        term "Cobalt",
        qual {
          {
            subh "pharmacology"
          }
        }
      },
      {
        term "Electrophoretic Mobility Shift Assay"
      },
      {
        term "Enzyme-Linked Immunosorbent Assay"
      },
      {
        term "Eye Proteins",
        qual {
          {
            subh "genetics"
          },
          {
            mp TRUE,
            subh "metabolism"
          }
        }
      },
      {
        term "Guinea Pigs"
      },
      {
        term "Hypoxia-Inducible Factor 1, alpha Subunit",
        qual {
          {
            subh "metabolism"
          }
        }
      },
      {
        term "Nerve Growth Factors",
        qual {
          {
            subh "genetics"
          },
          {
            mp TRUE,
            subh "metabolism"
          }
        }
      },
      {
        term "Neuroglia",
        qual {
          {
            mp TRUE,
            subh "physiology"
          }
        }
      },
      {
        term "RNA, Messenger",
        qual {
          {
            subh "metabolism"
          }
        }
      },
      {
        term "RNA, Small Interfering",
        qual {
          {
            subh "pharmacology"
          }
        }
      },
      {
        term "Rats"
      },
      {
        term "Retina",
        qual {
          {
            subh "cytology"
          }
        }
      },
      {
        term "Serpins",
        qual {
          {
            subh "genetics"
          },
          {
            mp TRUE,
            subh "metabolism"
          }
        }
      },
      {
        term "Up-Regulation",
        qual {
          {
            subh "drug effects"
          },
          {
            mp TRUE,
            subh "physiology"
          }
        }
      },
      {
        term "Vascular Endothelial Growth Factor A",
        qual {
          {
            subh "metabolism"
          }
        }
      }
    },
    substance {
      {
        type nameonly,
        name "Eye Proteins"
      },
      {
        type nameonly,
        name "Hif1a protein, rat"
      },
      {
        type nameonly,
        name "Hypoxia-Inducible Factor 1, alpha Subunit"
      },
      {
        type nameonly,
        name "Nerve Growth Factors"
      },
      {
        type nameonly,
        name "RNA, Messenger"
      },
      {
        type nameonly,
        name "RNA, Small Interfering"
      },
      {
        type nameonly,
        name "Serpins"
      },
      {
        type nameonly,
        name "Vascular Endothelial Growth Factor A"
      },
      {
        type nameonly,
        name "pigment epithelium-derived factor"
      },
      {
        type cas,
        cit "7440-48-4",
        name "Cobalt"
      },
      {
        type cas,
        cit "7646-79-9",
        name "cobaltous chloride"
      }
    },
    pmid 21922517,
    pub-type {
      "Journal Article"
    },
    status medline
  }
}

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