Oxidative stress induces vascular heme oxygenase-1 expression in ovariectomized rats

Yen Mei Lee, Pao Yun Cheng, Su Fen Hong, Shu Ying Chen, Kwok Keung Lam, Joen Rong Sheu, Mao Hsiung Yen

研究成果: 雜誌貢獻文章同行評審

39 引文 斯高帕斯(Scopus)


Heme oxygenase-1 (HO-1), an inducible stress protein, has been implicated in cytoprotection against oxidative stress in vitro and in vivo. Estrogens also have antioxidant effects. This study investigated the time course of HO-1 and inducible nitric oxide synthase (iNOS) expression in the aortas of ovariectomized rats, and the regulatory relationship between the NO/NOS and the carbon monoxide/HO systems. HO-1 and iNOS protein expression was induced by ovariectomy (Ovx) and was extremely high 2-6 weeks after Ovx compared with the sham-operated group. Expression of the constitutive enzymes HO-2 and endothelial NOS did not differ significantly between sham-operated and Ovx rats. 17β-Estradiol (E2) replacement reversed these changes in rats after Ovx. Long-term treatment with the antioxidant tempol significantly inhibited HO-1 and iNOS expression. The iNOS inhibitor aminoguanidine significantly suppressed the induction of HO-1. Oxidized glutathione in the hearts of Ovx rats increased gradually, with significant elevation at 3-6 weeks after Ovx compared with the sham-operated group, whereas plasma levels of NO metabolites were significantly reduced 4-6 weeks after Ovx. Treatment with the HO inhibitor zinc protoporphyrin IX blocked HO-1 induction, but significantly increased the plasma levels of NO metabolites. In conclusion, HO-1 is induced by oxidative stress resulting from E2 depletion. The NO/iNOS system contributes to the induction of HO-1, which may subsequently suppress iNOS activity to modulate vasculoprotective effects after menopause.

頁(從 - 到)108-117
期刊Free Radical Biology and Medicine
出版狀態已發佈 - 7月 1 2005

ASJC Scopus subject areas

  • 醫藥 (全部)
  • 毒理學
  • 臨床生物化學


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