NDLI: Nitrogen monoxide-mediated control of ferritin synthesis: Implications for macrophage iron homeostasis

Content Provider	PubMed Central
Author	Kim, Sangwon Prem, Ponka
Copyright Year	2002
Abstract	Intracellular iron homeostasis is regulated posttranscriptionally by iron regulatory proteins 1 and 2 (IRP1 and IRP2). In the absence of iron in the labile pool, IRPs bind to specific nucleotide sequences called iron responsive elements (IREs), which are located in the 5′ untranslated region of ferritin mRNA and the 3′ untranslated region of transferrin receptor mRNA. IRP binding to the IREs suppresses ferritin translation and stabilizes transferrin receptor mRNA, whereas the opposite scenario develops in iron-replete cells. Binding of IRPs to the IREs is also affected by nitrogen monoxide (NO), but there are conflicting reports regarding the effect of NO on ferritin synthesis. In this study, we demonstrated that a short exposure of RAW 264.7 cells (a macrophage cell line) to the NO+ donor, sodium nitroprusside (SNP), resulted in a dramatic increase in ferritin synthesis. The SNP-mediated increase of ferritin synthesis could be blocked by MG132, an inhibitor of proteasome-dependent protein degradation, which also prevented the degradation of IRP2 caused by SNP treatment. Moreover, treatment of RAW 264.7 cells with IFN-γ and lipopolysaccharide caused IRP2 degradation and stimulated ferritin synthesis, changes that could be prevented by specific inhibitors of inducible nitric oxide synthase. Furthermore, the SNP-mediated increase in ferritin synthesis was associated with a significant enhancement of iron incorporation into ferritin. These observations indicate that NO+-mediated modulation of IRP2 plays an important role in controlling ferritin synthesis and iron metabolism in murine macrophages.
Related Links	http://dx.doi.org/10.1073/pnas.192316099
Ending Page	12219
Page Count	6
Starting Page	12214
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	19
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-09-17
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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