Repression of heme oxygenase-1 by hypoxia in vascular endothelial cells

Masaharu Nakayama, Kazuhiro Takahashi, Tomomi Kitamuro, Ken Ichi Yasumoto, Dai Katayose, Kunio Shirato, Yoshiaki Fujii-Kuriyama, Shigeki Shibahara

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82 Citations (Scopus)


Heme oxygenase 1 (HO-1), a rate-limiting enzyme in heme catabolism, has been reported to be induced by hypoxia. Unexpectedly, here we show that expression of HO-1 mRNA is repressed by hypoxia in primary cultures of human umbilical vein endothelial cells (HUVECs), but is increased by cobalt chloride (CoCl2) that is known to mimic hypoxia. Under the culture conditions used, the DNA-binding and transactivation activities of hypoxia-inducible factor 1 were increased in HUVECs by hypoxia or CoCl2. Therefore, hypoxia and cobalt showed opposing effects on HO-1 mRNA expression, despite activation of hypoxia-inducible factor 1. The half-life of HO-1 mRNA was not changed by hypoxia, but was significantly prolonged by CoCl2. Hypoxia also represses HO-1 mRNA expression in human coronary artery endothelial cells and astrocytes. The repression of HO-1 expression may represent the adaptation to hypoxia in certain cell types. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)665-671
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - 2000 May 19


  • Bilirubin
  • Cobalt
  • Desferrioxamine
  • Endothelial cells
  • Heme
  • Hypoxia-inducible factor
  • Oxygen sensor
  • Stress response


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