title: Regulation of endothelial heme oxygenase activity during hypoxia is dependent on chelatable iron.
abstract: The regulation of heme oxygenase (HO) activity and its dependence on iron was studied in bovine aortic endothelial cells (BAEC) subjected to hypoxia-reoxygenation (H/R). HO activity was induced by hypoxia (10 h) and continued to increase during the reoxygenation phase. HO-1 protein levels were strongly induced by hypoxia from undetectable levels and remained elevated at least 8 h postreoxygenation. Addition of the Fe(3+) chelator desferrioxamine mesylate (DFO) or the Fe(2+) chelator o-phenanthroline during hypoxia alone or during the entire H/R period inhibited the induction of HO activity and HO-1 protein levels. However, DFO had no effect and o-phenanthroline had a partial inhibitory effect on HO activity and protein levels when added only during reoxygenation. Loading of BAEC with Fe(3+) enhanced the activation of the HO-1 gene by H/R, whereas loading with L-aminolevulinic acid, which stimulates heme synthesis, had little effect. These results suggest that chelatable iron participates in regulating HO expression during hypoxia.
authors.affiliation: Department of Medicine, Southern Illinois University School of Medicine, Springfield, Illinois 62794, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Ryter
authors.forename: M
authors.initials: M
authors.lastname: Si
authors.forename: C C
authors.initials: CC
authors.lastname: Lai
authors.forename: C Y
authors.initials: CY
authors.lastname: Su
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000622:Aminolevulinic Acid / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002248:Carbon Monoxide / Q000378:metabolism; D002417:Cattle; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D005290:Ferric Compounds / Q000378:metabolism / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D000860:Hypoxia / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010618:Phenanthrolines / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D005290:Ferric Compounds; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D010618:Phenanthrolines; D017319:Photosensitizing Agents; D000644:Quaternary Ammonium Compounds; D002248:Carbon Monoxide; D000622:Aminolevulinic Acid; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D003676:Deferoxamine; C013531:ferric ammonium citrate; C025205:1,10-phenanthroline; D000111:Acetylcysteine