Biosynthesis of nitric oxide activates iron regulatory factor in macrophages - PubMed (original) (raw)

Biosynthesis of nitric oxide activates iron regulatory factor in macrophages

J C Drapier et al. EMBO J. 1993 Sep.

Abstract

Biosynthesis of nitric oxide (NO) from L-arginine modulates activity of iron-dependent enzymes, including mitochondrial acontiase, an [Fe-S] protein. We examined the effect of NO on the activity of iron regulatory factor (IRF), a cytoplasmic protein which modulates both ferritin mRNA translation and transferrin receptor mRNA stability by binding to specific mRNA sequences called iron responsive elements (IREs). Murine macrophages were activated with interferon-gamma and lipopolysaccharide to induce NO synthase activity and cultured in the presence or absence of NG-substituted analogues of L-arginine which served as selective inhibitors of NO synthesis. Measurement of the nitrite concentration in the culture medium was taken as an index of NO production. Mitochondria-free cytosols were then prepared and aconitase activity as well as IRE binding activity and induction of IRE binding activity were correlated and depended on NO synthesis after IFN-gamma and/or LPS stimulation. Authentic NO gas as well as the NO-generating compound 3-morpholinosydnonimine (SIN-1) also conversely modulated aconitase and IRE binding activities of purified recombinant IRF. These results provide evidence that endogenously produced NO may modulate the post-transcriptional regulation of genes involved in iron homeostasis and support the hypothesis that the [Fe-S] cluster of IRF mediates iron-dependent regulation.

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References

1. 1. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):444-8 - PubMed
2. 1. Nucleic Acids Res. 1992 Jan 11;20(1):33-9 - PubMed
3. 1. Biochemistry. 1992 Mar 24;31(11):2847-9 - PubMed
4. 1. J Immunol. 1993 Feb 15;150(4):1509-16 - PubMed
5. 1. Nucleic Acids Res. 1993 Mar 25;21(6):1467-71 - PubMed

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