1. Oxidative stress induces vascular heme oxygenase-1 expression in ovariectomized rats
- Author
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Yen-Mei Lee, Su Fen Hong, Mao Hsiung Yen, Kwok Keung Lam, Pao Yun Cheng, Shu-Ying Chen, and Joen Rong Sheu
- Subjects
medicine.medical_specialty ,Antioxidant ,Time Factors ,Nitric Oxide Synthase Type III ,medicine.medical_treatment ,Ovariectomy ,Nitric Oxide Synthase Type II ,Protoporphyrins ,Aorta, Thoracic ,Endothelial NOS ,medicine.disease_cause ,Biochemistry ,Guanidines ,Nitric oxide ,Cyclic N-Oxides ,chemistry.chemical_compound ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Heat-Shock Proteins ,Nitrites ,Nitrates ,biology ,Estradiol ,Glutathione Disulfide ,Body Weight ,Ovary ,Uterus ,Organ Size ,Cytoprotection ,Rats ,Nitric oxide synthase ,Heme oxygenase ,Oxidative Stress ,Endocrinology ,chemistry ,Enzyme Induction ,Heme Oxygenase (Decyclizing) ,Ovariectomized rat ,biology.protein ,Oxygenases ,Female ,Spin Labels ,Nitric Oxide Synthase ,Oxidative stress - Abstract
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.
- Published
- 2004