Heme Oxygenase-1 Gene Expression Attenuates Angiotensin II-Mediated DNA Damage in Endothelial Cells
| Autor: | Alvin I. Goodman, Nader G. Abraham, Angelo Vanella, Gabriella Lombardo, Francesco Mazza |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
0301 basic medicine
Metalloporphyrins DNA damage Genetic Vectors medicine.disease_cause General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Humans Enzyme Inhibitors Heme Cells Cultured Cell Size Biliverdin Angiotensin II Biliverdine Membrane Proteins Hydrogen Peroxide Glutathione Oxidants Molecular biology Comet assay Heme oxygenase Oxidative Stress Retroviridae 030104 developmental biology chemistry 030220 oncology & carcinogenesis Heme Oxygenase (Decyclizing) Comet Assay Endothelium Vascular Heme Oxygenase-1 Oxidative stress DNA Damage |
| Zdroj: | Experimental Biology and Medicine. 228:576-583 |
| ISSN: | 1535-3699 1535-3702 |
| DOI: | 10.1177/15353702-0322805-31 |
| Popis: | Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin with the release of iron and carbon monoxide. HO-1 is inducible by inflammatory conditions, which cause oxidative stress in endothelial cells. Overexpression of human HO-1 in endothelial cells may have the potential to provide protection against a variety of agents that cause oxidative stress. We investigated the physiological significance of human HO-1 overexpression using a retroviral vector on attenuation of angiotensin II (Ang II)-mediated oxidative stress. Comet and glutathione (GSH) levels were used as indicators of the levels of oxidative stress. Comet assay was performed to evaluate damage on DNA, whereas GSH levels were measured to determine the unbalance of redox potential. Pretreatments with inducers, such as heme 10 μM, SnCl210 μM, and inhibitors, such as tin-mesoporphyrin 10 μM was followed by treatment with Ang II 200 ng/ml. Pretreatment with heme or SnCl2provoked significant reductions ( P < 0.01) of tail moment in the comet assay. Opposite effects were evident by pretreatment for 16 hr with tin-mesoporphyrin. A decrease in tail moment levels was found in human endothelial cells transduced with the human HO-1 gene. The addition of Ang II (200 ng/ml) to human dermal microvessel endothelial cel1-1 for 16 hr resulted in a significant ( P < 0.05) reduction of GSH contents control endothelial cells but not in endothelial cells transduced with HO-1 gene. The results presented indicated that stimulation or overexpression of HO-1 attenuated DNA damages caused by exposures of Ang II. |
| Databáze: | OpenAIRE |
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