Cellular pool of transient ferric iron, chelatable by deferoxamine and distinct from ferritin, that is involved in oxidative cell injury.
A cellular pool of transient ferric iron that is chelatable by deferoxamine, distinct from ferritin, and required for oxidative cell injury has been identified in cultured rat hepatocytes labeled with 59FeCl3. Pretreatment of hepatocytes with deferoxamine depleted the cellular pool of chelatable iron and protected the cells from an oxidative injury. Incubation of deferoxamine-pretreated hepatocytes in serum-free medium restored both the chelatable iron pool and the susceptibility to oxidative injury. Furthermore, inhibition of protein degradation with chymostatin prevented the restoration of both the chelatable pool and susceptibility to oxidative injury. The deferoxamine-chelatable iron pool was distinguished kinetically and immunochemically from the larger cellular pool of ferritin iron. The labeled iron in the deferoxamine-chelatable pool was transient, unlike either the total cellular uptake of 59Fe or its incorporation into ferritin, both of which increased with time of labeling. With pulse-chase labeling, the percentage of the total uptake of 59Fe that was represented by the deferoxamine-chelatable pool decreased. At the same time, the percentage represented by radioactivity immunoprecipitable as ferritin increased. Furthermore, immunoprecipitation of ferritin from the labeled lysates enriched the resulting immunosupernatants in deferoxamine-chelatable iron. The degree of enrichment for chelatable iron correlated with the percentage of the cellular label that was immunoprecipitable as ferritin. The deferoxamine-chelatable iron appears to represent a metabolically common pool of iron that is rapidly in transit through the cell. Extracellular iron entering the pool can be utilized for heme synthesis or stored in ferritin, whereas protein degradation releases storage iron into this pool.
Rothman
R J
RJ
Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Serroni
A
A
Farber
J L
JL
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D003676:Deferoxamine / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry / Q000633:toxicity*; D005293:Ferritins / Q000737:chemistry; D066298:In Vitro Techniques; D007502:Iron Chelating Agents / Q000737:chemistry; D008099:Liver / Q000166:cytology / Q000187:drug effects; D010084:Oxidation-Reduction; D010545:Peroxides / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D020122:tert-Butylhydroperoxide
D005290:Ferric Compounds; D007502:Iron Chelating Agents; D010545:Peroxides; D005293:Ferritins; D020122:tert-Butylhydroperoxide; D003676:Deferoxamine