Role of nitric oxide in cellular iron metabolism

Sangwon Kim, Prem Ponka

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)125-135
Number of pages11
JournalBioMetals
Volume16
Issue number1
DOIs
StatePublished - Mar 2003
Externally publishedYes

Fingerprint

Transferrin Receptors
Nitric oxide
Metabolism
transferrin
nitric oxide
Nitric Oxide
Iron
iron
metabolism
receptors
RNA
Messenger RNA
Interferons
Ferritins
Degradation
ferritin
interferons
Lipopolysaccharides
Iron Regulatory Protein 2
lipopolysaccharides

ASJC Scopus subject areas

  • Biomaterials
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Metals and Alloys

Cite this

Role of nitric oxide in cellular iron metabolism. / Kim, Sangwon; Ponka, Prem.

In: BioMetals, Vol. 16, No. 1, 03.2003, p. 125-135.

Research output: Contribution to journalArticle

Kim, Sangwon ; Ponka, Prem. / Role of nitric oxide in cellular iron metabolism. In: BioMetals. 2003 ; Vol. 16, No. 1. pp. 125-135.
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