title: Hypoxic induction of adrenomedullin in cultured human umbilical vein endothelial cells.
abstract: OBJECTIVE
  The current study evaluated the hypoxic induction of adrenomedullin gene expression and secretion, and its mechanism in cultured human umbilical vein endothelial cells (HUVEC).
  
  
  METHODS
  HUVEC were exposed to hypoxia or normoxia as controls for 1 to 24 h. Using Northern blot analysis and a radioimmunoassay, we evaluated adrenomedullin expression in HUVEC. The transcriptional component of adrenomedullin gene regulation was assessed by nuclear run-off experiments, and adrenomedullin mRNA half-life was measured by actinomycin D experiments.
  
  
  RESULTS
  We found that hypoxic conditions (1-3% oxygen) significantly increased adrenomedullin mRNA and protein in HUVEC. This increase was inversely proportional to oxygen tension and was reversible upon re-exposure to a 21% oxygen environment Nuclear run-off experiments revealed the enhanced transcriptional rate of adrenomedullin gene. Next, actinomycin D experiments revealed the enhanced adrenomedullin mRNA stability.
  
  
  CONCLUSIONS
  These results indicate that hypoxia increases adrenomedullin gene expression and secretion in HUVEC by transcriptional and post-transcriptional mechanisms. Hypoxic induction of adrenomedullin may play a pathophysiological role in the vascular systems.
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Tokyo, Japan. ogita-tky@umin.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Ogita
authors.forename: E
authors.initials: E
authors.lastname: Hashimoto
authors.forename: M
authors.initials: M
authors.lastname: Yamasaki
authors.forename: T
authors.initials: T
authors.lastname: Nakaoka
authors.forename: R
authors.initials: R
authors.lastname: Matsuoka
authors.forename: Y
authors.initials: Y
authors.lastname: Kira
authors.forename: T
authors.initials: T
authors.lastname: Fujita
mesh_terms: D053607:Adrenomedullin; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D014158:Transcription, Genetic; D014471:Umbilical Veins / Q000378:metabolism* / Q000473:pathology
chemical_list: D010455:Peptides; D012333:RNA, Messenger; D053607:Adrenomedullin