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Blood, Vol. 95 No. 9 (May 1), 2000:
pp. 2960-2966
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
Pawel Lipi ski,
Jean-Claude Drapier,
Leonor Oliveira,
Hanna Retmaska,
Barbara Sochanowicz, and
Marcin Kruszewski
From the Department of Molecular Biology, Institute of
Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzebiec,
Poland; the Institut de Chimie des Substances Naturelles, CNRS,
Gif-sur-Yvette, France; and the Department of Radiobiology and Health
Protection, Institute of Nuclear Chemistry and Technology, Warsaw,
Poland.
The redox properties of iron make this metal a key participant in
oxygen-mediated toxicity. Accordingly, L5178Y (LY) mouse lymphoma cell
lines, which display a unique inverse cross-sensitivity to ionizing
radiation (IR) and hydrogen peroxide (H2O2),
are a suitable model for the study of possible differences in the
constitutive control of intracellular iron availability. We report here
that the level of iron in the cytosolic labile iron pool (LIP), ie, potentially active in the Fenton reaction, is more than 3-fold higher
in IR-resistant, H2O2-sensitive (LY-R) cells
than in IR-sensitive, H2O2-resistant (LY-S)
cells. This difference is associated with markedly greater content of
ferritin H-subunits (H-Ft) in LY-S than in LY-R cells. Our results show
that different expression of H-Ft in LY cells is a consequence of an
up-regulation of H-Ft mRNA in the LY-S mutant cell line. In contrast,
posttranscriptional control of iron metabolism mediated by
iron-responsive element-iron regulatory proteins (IRPs) interaction is
similar in the 2 cell lines, although IRP1 protein levels in iron-rich
LY-R cells are twice those in iron-deficient LY-S cells. In showing
that LY cell lines exhibit 2 different patterns of intracellular iron
regulation, our results highlight both the role of high LIP in the
establishment of pro-oxidant status in mammalian cells and the
antioxidant role of ferritin.
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