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Blood, Vol. 94 No. 6 (September 15), 1999:
pp. 2128-2134
The Cellular Labile Iron Pool and Intracellular Ferritin in K562 Cells
Abraham M. Konijn,
Hava Glickstein,
Boris Vaisman,
Esther G. Meyron-Holtz,
Itzchak N. Slotki, and
Z. Ioav Cabantchik
From the Department of Human Nutrition and Metabolism, Faculty of
Medicine, and Department of Biological Chemistry, Institute of Life
Sciences, Hebrew University of Jerusalem and Nephrology Unit, Shaare
Zedek Medical Center, Jerusalem, Israel.
The labile iron pool (LIP) harbors the metabolically active and
regulatory forms of cellular iron. We assessed the role of intracellular ferritin in the maintenance of intracellular LIP levels.
Treating K562 cells with the permeant chelator isonicotinoyl salicylaldehyde hydrazone reduced the LIP from 0.8 to 0.2 µmol/L, as
monitored by the metalo-sensing probe calcein. When cells were reincubated in serum-free and chelator-free medium, the LIP partially recovered in a complex pattern. The first component of the LIP to
reappear was relatively small and occurred within 1 hour, whereas the
second was larger and relatively slow to occur, paralleling the decline
in intracellular ferritin level (t1/2= 8 hours). Protease inhibitors such as leupeptin suppressed both the changes in ferritin levels and cellular LIP recovery after chelation. The changes in the
LIP were also inversely reflected in the activity of iron regulatory
protein (IRP). The 2 ferritin subunits, H and L, behaved qualitatively
similarly in response to long-term treatments with the iron chelator
deferoxamine, although L-ferritin declined more rapidly, resulting in a
4-fold higher H/L-ferritin ratio. The decline in L-ferritin, but not
H-ferritin, was partially attenuated by the lysosomotrophic agent,
chloroquine; on the other hand, antiproteases inhibited the degradation
of both subunits to the same extent. These findings indicate that,
after acute LIP depletion with fast-acting chelators, iron can be
mobilized into the LIP from intracellular sources. The underlying
mechanisms can be kinetically analyzed into components associated with
fast release from accessible cellular sources and slow release from
cytosolic ferritin via proteolysis. Because these iron forms are known
to be redox-active, our studies are important for understanding the
biological effects of cellular iron chelation.
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