Antioxidant mechanism of heme oxygenase-1 involves an increase in superoxide dismutase and catalase in experimental diabetes

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 58; no. 2; pp. H701 - H707
• Main Authors: TURKSEVEN, Saadet, KRUGER, Adam, MINGONE, Christopher J, KAMINSKI, Pawel, INABA, Muneo, RODELLA, Luigi F, IKEHARA, Susumu, WOLIN, Michael S, ABRAHAM, Nader G
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Physiological Society 01.08.2005
• Subjects: Antioxidants; Biological and medical sciences; Circulatory system; Diabetes; Enzymes; Fundamental and applied biological sciences. Psychology; Proteins; Rodents; Vertebrates: cardiovascular system; Endocrinopathy; Oxidative stress; Enzyme; Diabetes mellitus; Heme oxygenase (decyclizing); Superoxide dismutase; antioxidant enzymes; Antioxidant; Extracellular; endothelial dysfunction; Nitric-oxide synthase; Endothelium; Vertebrata; Mammalia; Peroxidases; Catalase; Dysfunction; Oxidoreductases; Circulatory system; extracellular superoxide dismutase; nitric oxide synthase; superoxide
• ISSN: 0363-6135; 1522-1539

Increased heme oxygenase (HO)-1 activity attenuates endothelial cell apoptosis and decreases superoxide anion (O2-) formation in experimental diabetes by unknown mechanisms. We examined the effect of HO-1 protein and HO activity on extracellular SOD (EC-SOD), catalase, O2-, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) levels and vascular responses to ACh in control and diabetic rats. Vascular EC-SOD and plasma catalase activities were significantly reduced in diabetic compared with nondiabetic rats (P < 0.05). Upregulation of HO-1 expression by intermittent administration of cobalt protoporphyrin, an inducer of HO-1 protein and activity, resulted in a robust increase in EC-SOD but no significant change in Cu-Zn-SOD. Administration of tin mesoporphyrin, an inhibitor of HO-1 activity, decreased EC-SOD protein. Increased HO-1 activity in diabetic rats was associated with a decrease in iNOS but increases in eNOS and plasma catalase activity. On the other hand, aortic ring segments from diabetic rats exhibited a significant reduction in vascular relaxation to ACh, which was reversed with cobalt protoporphyrin treatment. These data demonstrate that an increase in HO-1 protein and activity, i.e., CO and bilirubin production, in diabetic rats brings about a robust increase in EC-SOD, catalase, and eNOS with a concomitant increase in endothelial relaxation and a decrease in O2-. These observations in experimental diabetes suggest that the vascular cytoprotective mechanism of HO-1 against oxidative stress requires an increase in EC-SOD and catalase. [PUBLICATION ABSTRACT]