Can Cellular Labile Iron Pool be Considered Solely a Pro‐oxidant Species in Cells?

Abstract

The ubiquitous cellular labile iron pool (LIP) is often associated with the production of the highly reactive species hydroxyl radical, which forms through redox reaction with hydrogen peroxide. Several studies indicate that LIP‐dependent hydroxyl radical production causes cellular damage through oxidation of biomolecules. Although LIP's interaction with hydrogen peroxide and its effects are well established, the interaction of LIP and peroxynitrite, and it's effects are not yet understood. Does peroxynitrite, a potent oxidant species known to interact with transition metals, act as an oxidant species in cells just like hydrogen peroxide? In murine macrophage cells we observed that removal of LIP with membrane‐permeable iron chelators attenuates peroxynitrite‐dependent oxidation and nitrosation of fluorescent probes in both normal and oxidative stress conditions which is in stark contrast to H2O2‐dependent oxidation. These results could not be reproduced in cell‐free systems indicating that the chelator‐enhancing effect on peroxynitrite‐dependent modifications of the probes depend on cells constituents, presumably including LIP, that reacts with these chelators. It is also observed that neither free nor ferrous‐complexed chelators stimulated intracellular or extracellular nitrosative and oxidative processes. These results indicates that LIP is a competitive cellular target for peroxynitrite and its derived oxidants, and thereby reduces oxidative processes, which may change the current view of LIP as a cellular source of pro‐oxidant iron.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Protective Effect of Dinitrosyl Iron Complexes Bound with Hemoglobin on Oxidative Modification by Peroxynitrite

“…It was suggested that LIP intercepts ONOO − and its free radical derivatives, e.g., • NO 2 and • CO 3 [60]. The antioxidant effect of bivalent iron for peroxynitrite is explained by its ability to reduce ONOO − to nitrite by two-electron mechanism, with a rate constant being two orders higher than that of ONOO − reaction with CO 2 [58,61].…”