Nitrosothiol Formation and Protection against Fenton Chemistry by Nitric Oxide-induced Dinitrosyliron Complex Formation from Anoxia-initiated Cellular Chelatable Iron Increase*
| Autor: | Aashka R. Patel, Qian Li, Harry K. Mahtani, Chuanyu Li, Jack R. Lancaster, Jian Du |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Iron
chemistry.chemical_element Deferoxamine Iron Chelating Agents Nitric Oxide Biochemistry Oxygen Nitric oxide Cell Line chemistry.chemical_compound Mice medicine Animals Hydrogen peroxide Molecular Biology chemistry.chemical_classification Reactive oxygen species S-Nitrosothiols Macrophages Electron Spin Resonance Spectroscopy Cell Biology Hydrogen Peroxide Cell Hypoxia chemistry Thiol Nitrogen Oxides Reactive Oxygen Species Intracellular Molecular Biophysics medicine.drug |
| Popis: | Dinitrosyliron complexes (DNIC) have been found in a variety of pathological settings associated with (•)NO. However, the iron source of cellular DNIC is unknown. Previous studies on this question using prolonged (•)NO exposure could be misleading due to the movement of intracellular iron among different sources. We here report that brief (•)NO exposure results in only barely detectable DNIC, but levels increase dramatically after 1-2 h of anoxia. This increase is similar quantitatively and temporally with increases in the chelatable iron, and brief (•)NO treatment prevents detection of this anoxia-induced increased chelatable iron by deferoxamine. DNIC formation is so rapid that it is limited by the availability of (•)NO and chelatable iron. We utilize this ability to selectively manipulate cellular chelatable iron levels and provide evidence for two cellular functions of endogenous DNIC formation, protection against anoxia-induced reactive oxygen chemistry from the Fenton reaction and formation by transnitrosation of protein nitrosothiols (RSNO). The levels of RSNO under these high chelatable iron levels are comparable with DNIC levels and suggest that under these conditions, both DNIC and RSNO are the most abundant cellular adducts of (•)NO. |
| Databáze: | OpenAIRE |
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