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Medientyp:
E-Artikel
Titel:
Mammalian Tissue Oxygen Levels Modulate Iron-Regulatory Protein Activities in Vivo
Beteiligte:
Meyron-Holtz, Esther G.;
Ghosh, Manik C.;
Rouault, Tracey A.
Erschienen:
American Association for the Advancement of Science (AAAS), 2004
Erschienen in:Science
Sprache:
Englisch
DOI:
10.1126/science.1103786
ISSN:
0036-8075;
1095-9203
Entstehung:
Anmerkungen:
Beschreibung:
<jats:p>
The iron-regulatory proteins (IRPs) posttranscriptionally regulate expression of transferrin receptor, ferritin, and other iron metabolism proteins. Although both IRPs can regulate expression of the same target genes, IRP2
<jats:sup>–/–</jats:sup>
mice significantly misregulate iron metabolism and develop neurodegeneration, whereas IRP1
<jats:sup>–/–</jats:sup>
mice are spared. We found that IRP2
<jats:sup>–/–</jats:sup>
cells misregulated iron metabolism when cultured in 3 to 6% oxygen, which is comparable to physiological tissue concentrations, but not in 21% oxygen, a concentration that activated IRP1 and allowed it to substitute for IRP2. Thus, IRP2 dominates regulation of mammalian iron homeostasis because it alone registers iron concentrations and modulates its RNA-binding activity at physiological oxygen tensions.
</jats:p>