Mammalian Tissue Oxygen Levels Modulate Iron-Regulatory Protein Activities in Vivo

American Association for the Advancement of Science (AAAS) - Tập 306 Số 5704 - Trang 2087-2090 - 2004
Esther G. Meyron‐Holtz1, Manik C. Ghosh1, Tracey A. Rouault1
1Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892 USA

Tóm tắt

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 –/– mice significantly misregulate iron metabolism and develop neurodegeneration, whereas IRP1 –/– mice are spared. We found that IRP2 –/– 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.

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Materials and methods are available as supporting material on Science Online.

This work was supported by the intramural program of the National Institute of Child Health and Human Development and in part by the Lookout Foundation.

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American Association for the Advancement of Science (AAAS)

Tập 306 Số 5704

2087-2090

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