title: Hypoxia controls iron metabolism and glutamate secretion in retinal pigmented epithelial cells.
abstract: BACKGROUND
  Blood-barrier systems are essential in controlling iron levels in organs such as the brain and eye, both of which experience hypoxia in pathological conditions. While hypoxia's effects on numerous iron regulatory and storage proteins have been studied, little is known about how hypoxia affects iron metabolism. Iron also controls glutamate production and secretion; therefore the effects of hypoxia on iron metabolism and glutamate secretion were studied in polarized retinal pigmented epithelial (RPE) cells.
  
  
  METHODS
  Primary canine RPE were cultured in Millicells to create polarized cell cultures. Iron uptake and efflux were measured in hypoxic and normoxic conditions. RPE were loaded with ⁵⁹Fe-transferrin. Glutamate concentrations in the cell conditioned media were also measured.
  
  
  RESULTS
  Hypoxia induced a large increase in iron efflux from RPE in the basolateral direction. Glutamate secretion occurred mainly in the basolateral direction which is away from the retina and out of the eye in vivo. Glutamate secretion was doubled under hypoxic conditions.
  
  
  CONCLUSIONS
  Hypoxia is known to induce oxidative damage. The current results show that iron, a key catalyst of free radical generation, is removed from RPE under hypoxic conditions which may help protect RPE from oxidative stress. Results obtained here indicate the importance of using polarized tight junctional cells as more physiologically relevant models for blood-barrier-like systems.
  
  
  CONCLUSIONS
  While the effects of hypoxia on iron efflux and glutamate secretion may be protective for RPE cells and retina, increased glutamate secretion in the brain could cause some of the damaging neurological effects seen in stroke.
authors: Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC 27607, USA.
authors: Jill
authors: J
authors: Harned
authors: Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC 27607, USA.
authors: Steven
authors: S
authors: Nagar
authors: Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC 27607, USA. Electronic address: chris_mcgahan@ncsu.edu.
authors: M Christine
authors: MC
authors: McGahan
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D010084:Oxidation-Reduction; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology; D020521:Stroke / Q000378:metabolism / Q000473:pathology
chemical_list: D018698:Glutamic Acid; D007501:Iron
keywords: Blood–ocular barriers; Glutamate; Hypoxia; Iron transport