Endothelial cell apoptosis is accelerated by inorganic iron and heat via an oxygen radical dependent mechanism
| Autor: | Ammini K. Jacob, Paul E. Swanson, Masako Hiramatsu, S. L. Demeester, J. Perren Cobb, Timothy G. Buchman, Irene E. Karl, Richard S. Hotchkiss |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Umbilical Veins
Programmed cell death Hot Temperature Sodium arsenite Free Radicals Cell Survival Deferoxamine Iron Chelating Agents Ferric Compounds Models Biological Superoxide dismutase chemistry.chemical_compound Chlorides Dichlorofluorescein medicine Humans Propidium iodide Heat shock Cells Cultured chemistry.chemical_classification Drug Carriers Reactive oxygen species biology business.industry Microcirculation Oxyquinoline Quaternary Ammonium Compounds Kinetics chemistry Biochemistry Biophysics biology.protein Ferric Surgery Endothelium Vascular Reactive Oxygen Species business Phenanthrolines medicine.drug |
| Zdroj: | Surgery. 122:243-254 |
| ISSN: | 0039-6060 |
| DOI: | 10.1016/s0039-6060(97)90015-5 |
| Popis: | Background. Iron participates in diverse pathologic processes by way of the Fenton reaction, which catalyzes the formation of reactive oxygen species (ROS). To test the hypothesis that this reaction accelerates apoptosis, we used human umbilical vein endothelial cells (HUVECs) as surrogates for the microvasculature in vivo. Methods. HUVECs were loaded with Fe [III](ferric chloride and ferric ammonium citrate) with 8-hydroxyquinoline as carrier and were then challenged with two stimuli of the heat shock response, authentic heat or sodium arsenite. Iron dependence was tested with two chelators, membrane-impermeable deferoxamine and membrane-permeable o-phenanthroline. The role of ROS was assessed with superoxide dismutase, catalase, and the reporter compound dichlorofluorescein diacetate. The mechanism of cell death was assessed with three complementary techniques, Annexin V/propidium iodide labeling, the TUNEL stain, and electron microscopy. Results. Iron-loaded HUVECs executed apoptosis after a heat shock stimulus. Iron-catalyzed formation of ROS appeared to be a critical mechanism, because both chelation of iron and enzymatic detoxification of ROS attenuated this apoptosis. Conclusions. Inorganic iron, in concert with chemical and physical inducers of the heat shock response, may trigger apoptosis. The accumulation of iron in injured tissue may thereby predispose to accelerated apoptosis and account, in part, for poor wound healing and organ failure. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect