Ryter S W, Si M, Lai C C, Su C Y
Department of Medicine, Southern Illinois University School of Medicine, Springfield, Illinois 62794, USA.
Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H2889-97. doi: 10.1152/ajpheart.2000.279.6.H2889.
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.
在经历缺氧复氧（H/R）的牛主动脉内皮细胞（BAEC）中，研究了血红素加氧酶（HO）活性的调节及其对铁的依赖性。缺氧（10小时）可诱导HO活性，且在复氧阶段持续升高。HO-1蛋白水平在缺氧时从不可检测的水平被强烈诱导，并且在复氧后至少8小时仍保持升高。在单独缺氧期间或整个H/R期间添加Fe(3+)螯合剂甲磺酸去铁胺（DFO）或Fe(2+)螯合剂邻菲罗啉可抑制HO活性和HO-1蛋白水平的诱导。然而，仅在复氧期间添加时，DFO对HO活性和蛋白水平无影响，邻菲罗啉有部分抑制作用。用Fe(3+)加载BAEC增强了H/R对HO-1基因的激活，而用刺激血红素合成的L-氨基乙酰丙酸加载则几乎没有影响。这些结果表明，可螯合的铁参与缺氧期间HO表达的调节。
