Cellular pool of transient ferric iron, chelatable by deferoxamine and distinct from ferritin, that is involved in oxidative cell injury

RJ Rothman, A Serroni and JL Farber

Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.

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.

Volume 42, Issue 4, pp. 703-710, 10/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				J. H. Park, K. T. Han, K.-J. Eu, J.-S. Kim, K. H. Chung, B. Park, G. S. Yang, K.-H. Lee, and M.-H. Cho Diffusion flame-derived fine particulate matters doped with iron caused genotoxicity in B6C3F1 mice Toxicology and Industrial Health, February 1, 2005; 21(1-2): 57 - 65. [Abstract] [PDF]

				S. Bunda, N. Kaviani, and A. Hinek Fluctuations of Intracellular Iron Modulate Elastin Production J. Biol. Chem., January 21, 2005; 280(3): 2341 - 2351. [Abstract] [Full Text] [PDF]

				B. Scheiber-Mojdehkar, B. Lutzky, R. Schaufler, B. Sturm, and H. Goldenberg Non-Transferrin-Bound Iron in the Serum of Hemodialysis Patients Who Receive Ferric Saccharate: No Correlation to Peroxide Generation J. Am. Soc. Nephrol., June 1, 2004; 15(6): 1648 - 1655. [Abstract] [Full Text] [PDF]

				D. Darbari, M. Loyevsky, V. Gordeuk, J. A. Kark, O. Castro, S. Rana, V. Apprey, and J. Kurantsin-Mills Fluorescence measurements of the labile iron pool of sickle erythrocytes Blood, July 1, 2003; 102(1): 357 - 364. [Abstract] [Full Text] [PDF]

				G. Buonocore, S. Perrone, M. Longini, P. Paffetti, P. Vezzosi, M. G. Gatti, and R. Bracci Non protein bound iron as early predictive marker of neonatal brain damage Brain, May 1, 2003; 126(5): 1224 - 1230. [Abstract] [Full Text] [PDF]

				P. Lipinski, J.-C. Drapier, L. Oliveira, H. Retmanska, B. Sochanowicz, and M. Kruszewski Intracellular iron status as a hallmark of mammalian cell susceptibility to oxidative stress: a study of L5178Y mouse lymphoma cell lines differentially sensitive to H2O2 Blood, May 1, 2000; 95(9): 2960 - 2966. [Abstract] [Full Text] [PDF]

				S. Epsztejn, H. Glickstein, V. Picard, I. N. Slotki, W. Breuer, C. Beaumont, and Z. I. Cabantchik H-Ferritin Subunit Overexpression in Erythroid Cells Reduces the Oxidative Stress Response and Induces Multidrug Resistance Properties Blood, November 15, 1999; 94(10): 3593 - 3603. [Abstract] [Full Text] [PDF]

				K. Kramer-Stickland, A. Edmonds, W. B. Bair III, and G.T. Bowden Inhibitory effects of deferoxamine on UVB-induced AP-1 transactivation Carcinogenesis, November 1, 1999; 20(11): 2137 - 2142. [Abstract] [Full Text] [PDF]

				A. M. Konijn, H. Glickstein, B. Vaisman, E. G. Meyron-Holtz, I. N. Slotki, and Z. I. Cabantchik The Cellular Labile Iron Pool and Intracellular Ferritin in K562 Cells Blood, September 15, 1999; 94(6): 2128 - 2134. [Abstract] [Full Text] [PDF]

				D. Howe and L. P. Mallavia Coxiella burnetii Infection Increases Transferrin Receptors on J774A.1 Cells Infect. Immun., July 1, 1999; 67(7): 3236 - 3241. [Abstract] [Full Text] [PDF]

				S. Fogg, A. Agarwal, H. S. Nick, and G. A. Visner Iron Regulates Hyperoxia-Dependent Human Heme Oxygenase 1 Gene Expression in Pulmonary Endothelial Cells Am. J. Respir. Cell Mol. Biol., April 1, 1999; 20(4): 797 - 804. [Abstract] [Full Text]

				A. Staubli and U. A. Boelsterli The labile iron pool in hepatocytes: prooxidant-induced increase in free iron precedes oxidative cell injury Am J Physiol Gastrointest Liver Physiol, June 1, 1998; 274(6): G1031 - G1037. [Abstract] [Full Text] [PDF]

				B. Vaisman, E. Fibach, and A. M. Konijn Utilization of Intracellular Ferritin Iron for Hemoglobin Synthesis in Developing Human Erythroid Precursors Blood, July 15, 1997; 90(2): 831 - 838. [Abstract] [Full Text] [PDF]

				W. Breuer, S. Epsztejn, and Z. I. Cabantchik Iron Acquired from Transferrin by K562 Cells Is Delivered into a Cytoplasmic Pool of Chelatable Iron(II) J. Biol. Chem., October 13, 1995; 270(41): 24209 - 24215. [Abstract] [Full Text] [PDF]