Arsenic induces oxidant stress and NF-kappa B activation in cultured aortic endothelial cells
| Autor: | Edward J. Dudek, Aaron Barchowsky, Melinda D. Treadwell, Karen E. Wetterhahn |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Arsenites
Swine Chromosomal translocation Biology medicine.disease_cause Biochemistry Antioxidants chemistry.chemical_compound Physiology (medical) medicine Animals Sulfhydryl Compounds Aorta Cells Cultured Arsenite Cell Nucleus DNA synthesis NF-kappa B NF-κB Glutathione DNA Hydrogen Peroxide Oxidants Molecular biology Sodium Compounds Endothelial stem cell Kinetics Oxidative Stress chemistry Endothelium Vascular Oxidative stress Intracellular |
| Zdroj: | Free radical biologymedicine. 21(6) |
| ISSN: | 0891-5849 |
| Popis: | Chronic exposure to low levels of environmentally derived arsenite are associated with vascular diseases, such as arteriosclerosis. However, the cellular and molecular mechanisms for vascular disease in response to arsenic are not known. These studies investigated the hypothesis that nonlethal levels of arsenic increase intracellular oxidant levels, promote nuclear translocation of trans-acting factors, and are mitogenic. Incubation of second passage vascular endothelial cells with less than 5 microM arsenite for 4 h increased incorporation of [3H]thymidine into genomic DNA, while higher concentrations failed to stimulate or inhibit DNA synthesis. Within 1 h following addition of noncytotoxic concentrations of arsenite, oxidants accumulated and thiol status increased. During this time period, there was increased nuclear retention of NF-kappa B binding proteins and nuclear translocation of NF-kappa B also occurred in response to 100 microM H2O2. Supershift analysis demonstrated that p65/p50 heterodimers accounted for the majority of proteins binding consensus kappa B sequences in cells treated with arsenite or oxidants. The antioxidants, N-acetylcysteine or dimethylfumaric acid, increased intracellular thiol status and prevented both oxidant formation and translocation of NF-kappa B binding proteins in response to arsenite. These data suggest that arsenite initiates vascular dysfunction by activating oxidant-sensitive endothelial cell signaling. |
| Databáze: | OpenAIRE |
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