title: Heme oxygenase-1 gene expression attenuates angiotensin II-mediated DNA damage in endothelial cells.
abstract: 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 microM, SnCl(2) 10 microM, and inhibitors, such as tin-mesoporphyrin 10 microM was followed by treatment with Ang II 200 ng/ml. Pretreatment with heme or SnCl(2) provoked 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 cell-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.
authors.affiliation: Department of Medicine and Pharmacology, New York Medical College, Valhalla, New York 10595, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mazza
authors.forename: Alvin
authors.initials: A
authors.lastname: Goodman
authors.forename: Gabriella
authors.initials: G
authors.lastname: Lombardo
authors.forename: Angelo
authors.initials: A
authors.lastname: Vanella
authors.forename: Nader G
authors.initials: NG
authors.lastname: Abraham
mesh_terms: D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D001664:Biliverdine / Q000378:metabolism; D048429:Cell Size; D002478:Cells, Cultured; D020552:Comet Assay; D004249:DNA Damage; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D005822:Genetic Vectors; D005978:Glutathione / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008565:Membrane Proteins; D008665:Metalloporphyrins / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D008665:Metalloporphyrins; D016877:Oxidants; C055421:tin mesoporphyrin; D000804:Angiotensin II; D006861:Hydrogen Peroxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D005978:Glutathione; D001664:Biliverdine