NDLI: Role of nitric oxide in cellular iron metabolism

Content Provider	Springer Nature Link
Author	Kim, Sangwon Ponka, Prem
Copyright Year	2003
Abstract	Iron regulatory proteins (IRP1 and IRP2) control the synthesis of transferrin receptors (TfR) and ferritin by binding to iron-responsive elements (IREs) which are located in the 3′ untranslated region (UTR) and the 5′ UTR of their respective mRNAs. Cellular iron levels affect binding of IRPs to IREs and consequently expression of TfR and ferritin. Moreover, NO•, a redox species of nitric oxide that interacts primarily with iron, can activate IRP1 RNA-binding activity resulting in an increase in TfR mRNA levels. We have shown that treatment of RAW 264.7 cells (a murine macrophage cell line) with NO+ (nitrosonium ion, which causes S-nitrosylation of thiol groups) resulted in a rapid decrease in RNA-binding of IRP2, followed by IRP2 degradation, and these changes were associated with a decrease in TfR mRNA levels. Moreover, we demonstrated that stimulation of RAW 264.7 cells with lipopolysaccharide (LPS) and interferon-γ (IFN-γ) increased IRP1 binding activity, whereas RNA-binding of IRP2 decreased and was followed by a degradation of this protein. Furthermore, the decrease of IRP2 binding/protein levels was associated with a decrease in TfR mRNA levels in LPS/IFN-γ-treated cells, and these changes were prevented by inhibitors of inducible nitric oxide synthase. These results suggest that NO+-mediated degradation of IRP2 plays a major role in iron metabolism during inflammation.
Starting Page	125
Ending Page	135
Page Count	11
File Format	PDF
ISSN	09660844
Journal	BioMetals
Volume Number	16
Issue Number	1
e-ISSN	15728773
Language	English
Publisher	Kluwer Academic Publishers
Publisher Date	2003-01-01
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Physical Chemistry Biochemistry
Content Type	Text
Resource Type	Article
Subject	Metals and Alloys Biochemistry, Genetics and Molecular Biology Biomaterials Agricultural and Biological Sciences

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