title: Protective Effects of Inducible HO-1 on Oxygen Toxicity in Rat Brain Endothelial Microvessel Cells.
abstract: BACKGROUND
  Reperfusion in ischemia is believed to generate cytotoxic oxidative stress, which mediates reperfusion injury. These stress conditions can initiate lipid peroxidation and damage to proteins, as well as promote DNA strand breaks. As biliverdin and bilirubin produced by heme oxygenase isoform 1 (HO-1) have antioxidant properties, the production of both antioxidants by HO-1 may help increase the resistance of the ischemic brain to oxidative stress. In the present study, the survival effect of HO-1 was confirmed using hemin.
  
  
  METHODS
  To confirm the roles of HO-1, carbon monoxide, and cyclic guanosine monophosphate further in the antioxidant effect of HO-1 and bilirubin, cells were treated with cycloheximide, desferoxamine, and zinc deuteroporphyrin IX 2,4 bis glycol, respectively.
  
  
  RESULTS
  HO-1 itself acted as an antioxidant. Furthermore, iron, rather than carbon monoxide, was involved in the HO-1-mediated survival effect. HO-1 activity was also important in providing bilirubin as an antioxidant.
  
  
  CONCLUSIONS
  Our results suggested that HO-1 helped to increase the resistance of the ischemic brain to oxidative stress.
authors.affiliation: Department of Brain Science, Graduate School, Daegu Gyeungbuk Institute of Science and Technology (DGIST), Daegu, Korea.
authors.forename: Seung-Jun
authors.initials: SJ
authors.lastname: Yoo
authors.affiliation: Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Neal K
authors.initials: NK
authors.lastname: Nakra
authors.affiliation: Department of Brain Science, Graduate School, Daegu Gyeungbuk Institute of Science and Technology (DGIST), Daegu, Korea. ; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. ; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. ; Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. ; Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Gabriele V
authors.initials: GV
authors.lastname: Ronnett
authors.affiliation: Department of Brain Science, Graduate School, Daegu Gyeungbuk Institute of Science and Technology (DGIST), Daegu, Korea.
authors.forename: Cheil
authors.initials: C
authors.lastname: Moon
keywords: Bilirubin; Carbon monoxide; Heme; Iron; Oxygenases