Deferoxamine-induced iron mobilization and redistribution of myocardial iron in cultured rat heart cells: studies of the chelatable iron pool by electron microscopy and Mössbauer spectroscopy.
Iron mobilization by deferoxamine from iron-loaded rat heart cells in culture was studied by electron microscopy and Mössbauer spectroscopy to identify 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 (less than 3.0 nm) recently acquired iron particles, which supports the "last-in, first-out" principle. Quantitation 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 transfer of cytosolic ferritin into siderosomes or, more likely, by increased mobilization of membrane-bound iron deposits from insoluble polynuclear 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.
Shiloh
H
H
Department of Pediatrics, Carmel Hospital, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
Iancu
T C
TC
Bauminger
E R
ER
Link
G
G
Pinson
A
A
Hershko
C
C
D000818:Animals; D002451:Cell Compartmentation; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology*; D005293:Ferritins / Q000378:metabolism; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism*; D008854:Microscopy, Electron; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D015204:Spectroscopy, Mossbauer
D005293:Ferritins; D007501:Iron; D003676:Deferoxamine