Iron mobilization by deferoxamine from iron-loaded rat heart cells in culture was studied by election microscopy and Mössbauer spectroscopy to identity the chelatable iron pool. Studies in which iron 59 was used have shown a diminishing response to deferoxamine with increasing time intervals, which suggests a gradual transit from a more available to a less available storage iron compartment. Mössbauer spectroscopy showed that practically all iron mobilized by deferoxamine was derived from the small (<3.0 nm) recently acquired iron particles, which supports the "last-in, flrstout" principle. Quantttation of cytosolic ferritin iron particles has shown a highly reproducible increase in cytosolic ferritin iron after deferoxamine treatment. This intracellular redistribution of iron stores is explained either by a reduced traraler of cytosolic ferritin into siderosomes or, more likely, by increased mobilization of membrane-bound iron deposits from insoluble polynuctear iron complexes in siderosomes and their subsequent incorporation into cytosolic ferritin. Thus the protective effect of deferoxamine on iron-loaded heart cells may be twofold: (1) net removal of excess iron by the formation of a stable complex of iron with deferoxamine and its secretion into the extracellular environment and (2) a shift of solubilized iron from membrane-bound deposits into the cytosol where iron is detoxified by its incorporation into the hollow shell of the ferritin protein.
|Original language||American English|
|Number of pages||9|
|State||Published - Apr 1992|