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Antioxidant mechanism of heme oxygenase-1 involves an increase in superoxide dismutase and catalase in experimental diabetes
Abstract
Increased heme oxygenase (HO)-1 activity attenuates endothelial cell apoptosis and decreases superoxide anion (O 2−) formation in experimental diabetes by unknown mechanisms. We examined the effect of HO-1 protein and HO activity on extracellular SOD (EC-SOD), catalase, O 2−, 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 O 2−. 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.
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“HO-1 improves endothelial dysfunction in diabetes (314) and has angiogenic properties (88).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [314]
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Metadata
- Authors
- Turkseven, S., Kruger, A., Mingone, C. J., Kaminski, P., Inaba, M., Rodella, L. F., Ikehara, S., Wolin, M. S., & Abraham, N. G.
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2005-08
- Volume
- 289
- Issue
- 2
- Pages
- H701-H707
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- OpenAlex
- W2160708843
- Cited by
- 256
- References
- 57
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 6 · 2022: 13 · 2021: 18 · 2020: 12 · 2019: 15 · 2018: 8 · 2017: 8 · 2016: 11 · 2015: 7 · 2014: 8 · 2013: 10 · 2012: 17
- FWCI
- 7.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01HL034300, HL 34300, HL55601)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Keywords
- heme oxygenase-1, superoxide dismutase, catalase, experimental diabetes, oxidative stress, endothelial nitric oxide synthase, inducible nitric oxide synthase, cobalt protoporphyrin, tin mesoporphyrin, endothelium-dependent relaxation, acetylcholine, vascular function, bilirubin, carbon monoxide, endothelial cell apoptosis
- MeSH terms
- Acetylcholine, Animals, Antioxidants, Aorta, Blood Vessels, Catalase, Cobalt, Diabetes Mellitus, Experimental, Endothelium, Vascular, Enzyme Induction, Heme Oxygenase (Decyclizing), Immunohistochemistry, Protoporphyrins, Superoxides, Superoxide Dismutase, Vasodilator Agents, Rats, Sprague-Dawley, Nitric Oxide Synthase, Rats, Heme Oxygenase-1, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III
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