title: Low- and high-dose hydrogen peroxide regulation of transcription factor NF-E2-related factor 2.
abstract: BACKGROUND
  Reactive oxygen species (ROS) may play both physiological and pathophysiological roles. Transcription factor NF-E2-related factor 2 (Nrf2) regulates antioxidant response element (ARE)-mediated genes expression and coordinates induction of chemoprotective proteins in response to physical and chemical stresses. The exact role of Nrf2 in cellular responses to different levels of oxidative stresses remains unknown.
  
  
  METHODS
  Rat pulmonary microvascular endothelial cells were cultured and treated with 0 mmol/L, 0.125 mmol/L, 0.25 mmol/L, 0.5 mmol/L, 1.0 mmol/L and 2.0 mmol/L hydrogen peroxide solution for 2 hours. Nrf2 gene expression was assayed by reverse transcription-PCR, Nrf2-ARE binding activity was assayed with electrophoretic mobility shift assay (EMSA), and localization of Nrf2 was detected with immunohistochemistry.
  
  
  RESULTS
  Low and moderate (0.125 mmol/L, 0.25 mmol/L and 0.5 mmol/L) doses hydrogen peroxide exposure of rat pulmonary microvascular endothelial cells led to the nuclear accumulation of Nrf2, increased activity of transcription regulation and up-regulation of ARE-medicated gene expression. In contrast, high doses of hydrogen peroxide (1 mmol/L, 2 mmol/L) exposure of the cells led to the nuclear exclusion of Nrf2, decreased activity transcription regulation and down-regulation of ARE-mediated gene expression.
  
  
  CONCLUSIONS
  Low and moderate doses of hydrogen peroxide play protective roles by increasing transcription activity of Nrf2, whereas high- dose hydrogen peroxide plays a deleterious role by decreasing transcription activity of Nrf2.
authors.affiliation: Department of Anesthesia, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jiao-lin
authors.initials: JL
authors.lastname: Ning
authors.forename: Li-wen
authors.initials: LW
authors.lastname: Mo
authors.forename: Xi-nan
authors.initials: XN
authors.lastname: Lai
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D015870:Gene Expression / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007150:Immunohistochemistry; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051267:NF-E2-Related Factor 2; D006861:Hydrogen Peroxide