http://www.eurekalert.org/pub_releases/2007-06/joci-jto053107.php
Iron imbalance in anemia: Hints from HIF
Iron is essential for red blood cell production and delivery of oxygen
to the body's tissues, and its supply is tightly regulated by hepcidin
- a small peptide expressed by the liver. Hepcidin upregulation, which
may occur in response to cancer or infection, blocks iron export from
cells via the only known iron exporter - ferroportin - as hepcidin
binding to ferroportin causes ferroportin internalization and
degradation. This block in iron export results in a condition known as
the anemia of chronic disease. Conversely, hepcidin downregulation is
associated with increased iron plasma levels and the iron overload
disorder hemochromatosis. In order to compensate for these imbalances,
hepcidin expression is increased by iron overload and decreased by
anemia, however the mechanisms that govern hepcidin's response to
these stimuli are not completely known. In a study appearing online on
June 7 in advance of publication in the July print issue of the
Journal of Clinical Investigation, Randall Johnson and colleagues from
University of California, San Diego, establish that the von Hippel-
Lindau/hypoxia-inducible transcription factor (VHL/HIF) pathway
provides an essential link between iron balance and hepcidin
regulation. They show that, in mice, anemia causes a drop in oxygen
availability to tissues, which in turn leads to decreased VHL-mediated
degradation of HIF-alpha. The increased HIF-alpha activity suppresses
hepcidin expression, causing increased ferroportin levels and serum
iron availability, in turn allowing increased red blood cell
production. The data suggest that inhibition of VHL could represent a
novel approach for the treatment of anemia of chronic disease.
TITLE: Regulation of iron homeostasis by the hypoxia-inducible
transcription factors (HIFs)
AUTHOR CONTACT:
Randall S. Johnson
University of California, San Diego, La Jolla, California, USA.
Phone : (858) 822-0509; Fax: (858) 822-5833; E-mail:
[email hidden]
Victor Nizet
University of California, San Diego, La Jolla, California, USA.
Phone: (858) 534-7408; Fax: (858) 534-5611: Email: [email hidden]
View the PDF of this article at: https://www.the-jci.org/article.php?id=31370
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