Extracellular Iron(II) Can Protect Cells from Hydrogen Peroxide

We hypothesized that exposure of cells to H2O2plus Fe2+would increase formation of cell-derived lipid peroxides that would inactivate prostaglandin H synthase, resulting in decreased prostaglandin synthesis. Therefore, we treated human endothelial cells with 0–100 μmH2O2followed immediately by addit...

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Bibliographic Details
Published in:Archives of biochemistry and biophysics 1996-06, Vol.330 (2), p.401-408
Main Authors: Hempel, Stephen L., Buettner, Garry R., Wessels, Duane A., Galvan, George M., O'Malley, Yunxia Q.
Format: Article
Language:English
Subjects:
Cells, Cultured
Cyclooxygenase Inhibitors - pharmacology
electron paramagnetic resonance
Endothelium, Vascular - drug effects
Endothelium, Vascular - metabolism
Epoprostenol - biosynthesis
Extracellular Space - metabolism
free radicals
Humans
Hydrogen Peroxide - toxicity
hydroxyl radical
Hydroxyl Radical - metabolism
Intracellular Fluid - metabolism
Iron - pharmacology
Lipid Peroxidation - drug effects
oxidant stress
Oxidative Stress
prostaglandin endoperoxide synthase
Prostaglandin-Endoperoxide Synthases - metabolism
prostaglandins
reactive oxygen species
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Summary:We hypothesized that exposure of cells to H2O2plus Fe2+would increase formation of cell-derived lipid peroxides that would inactivate prostaglandin H synthase, resulting in decreased prostaglandin synthesis. Therefore, we treated human endothelial cells with 0–100 μmH2O2followed immediately by addition of 0–200 μmFe2+. After oxidant exposure, cells were stimulated with 20 μmarachidonic acid to induce prostaglandin I2(PGI2) synthesis. Adding 100 μmH2O2prior to arachidonic acid decreased PGI2synthesis more than 80%. However, to our surprise, the addition of Fe2+, in increasing amounts, progressively protected PGI2synthesis against the harmful effects of H2O2. A ratio of one part H2O2to two parts Fe2+offered almost complete protection, whereas Fe3+did not protect PGI2synthesis from H2O2. We found that 100 μmH2O2was not cytolytic; however, 250 μmH2O2was cytolytic; Fe2+protected against this cytotoxicity. In addition, extracellular Fe2+prevented the rise in intracellular calcium caused by H2O2and extracellular Fe2+preserved intracellular glutathione in H2O2-exposed cells. Electron paramagnetic resonance spin trapping demonstrated that extracellular Fe2+generated the hydroxyl free radical, HO•, outside the cell. We speculate that extracellular Fe2+protects the intracellular space from H2O2by initiating the Fenton reaction outside the cell. This reductive cleavage of H2O2generates HO•in the extracellular space, where much of the HO•will react with noncellular components, thereby protecting the cell interior.
ISSN:0003-9861
1096-0384
DOI:10.1006/abbi.1996.0268