Newly delivered transferrin iron and oxidative cell injury.
Cell iron status was assessed in terms of its capacity to mediate cell injury by pro-oxidants. Cultured K562 cells, which maintain a stable cytosolic labile iron pool (LIP) of < 0.5 microM, underwent distinct changes after short exposures to transferrin (Tf) followed by t-butyl hydroperoxide (TBHP): (a) rise in LIP, detectable fluorimetrically; (b) increased lipid peroxidation and (c) eventual cell death. All of these effects were inhibited by weak bases or iron chelators. Similarly, hydrogen peroxide caused rises in both LIP and oxidant species detectable with 2',7'-dichlorofluorescin diacetate, which were enhanced by preincubation with Tf. The Tf-delivered iron disappeared from LIP and the TBHP-reactive pool with a t1/2 < 30 min. The results indicate that the catalytic potential of iron is highest while in transit between endosomes and cytosolic ligands.
Breuer
W
W
Department of Biological Chemistry, Institute of Life Sciences, Hebrew University of Jerusalem, Israel. BILLB@VMS.HUJI.AC.IL
Greenberg
E
E
Cabantchik
Z I
ZI
D002470:Cell Survival; D005452:Fluoresceins / Q000737:chemistry; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D010545:Peroxides / Q000494:pharmacology; D014168:Transferrin / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D020122:tert-Butylhydroperoxide
D005452:Fluoresceins; D007502:Iron Chelating Agents; D010545:Peroxides; D014168:Transferrin; C029569:diacetyldichlorofluorescein; D008315:Malondialdehyde; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D007501:Iron