Antioxidant mechanism of heme oxygenase-1 involves an increase in superoxide dismutase and catalase in experimental diabetes
| Autor: | Saadet Turkseven, Pawel M. Kaminski, Luigi Fabrizio Rodella, Adam Kruger, Nader G. Abraham, Michael S. Wolin, Susumu Ikehara, Muneo Inaba, Christopher J. Mingone |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Endothelium Nitric Oxide Synthase Type III Physiology Vasodilator Agents Nitric Oxide Synthase Type II Protoporphyrins Antioxidants Diabetes Mellitus Experimental Superoxide dismutase Rats Sprague-Dawley chemistry.chemical_compound Enos Superoxides Physiology (medical) Internal medicine medicine Animals Endothelial dysfunction Aorta biology Chemistry Superoxide Superoxide Dismutase Antioxidant enzymes Extracellular superoxide dismutase Nitric oxide synthase Oxidative stress Cobalt biology.organism_classification Catalase Immunohistochemistry Acetylcholine Rats Heme oxygenase medicine.anatomical_structure Endocrinology Enzyme Induction Heme Oxygenase (Decyclizing) biology.protein Blood Vessels Endothelium Vascular Nitric Oxide Synthase Cardiology and Cardiovascular Medicine Heme Oxygenase-1 |
| Zdroj: | American journal of physiology. Heart and circulatory physiology. 289(2) |
| ISSN: | 0363-6135 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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