Biosynthesis of nitric oxide activates iron regulatory factor in macrophages
| Autor: | H. Hirling, P Kaldy, J. Wietzerbin, Jean-Claude Drapier, L. C. Kühn |
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| Předmět: |
Lipopolysaccharides
Transferrin receptor RNA-binding protein Adenocarcinoma Arginine Nitric Oxide Aconitase General Biochemistry Genetics and Molecular Biology Nitric oxide Cell Line chemistry.chemical_compound Interferon-gamma Mice Gene expression Tumor Cells Cultured Animals Enzyme inducer Leukemia L1210 Molecular Biology Cells Cultured Nitrites Aconitate Hydratase Mice Inbred BALB C Mice Inbred C3H General Immunology and Microbiology biology General Neuroscience Iron-Regulatory Proteins Mammary Neoplasms Experimental RNA-Binding Proteins Macrophage Activation Recombinant Proteins Mitochondria Ferritin Nitric oxide synthase Kinetics Biochemistry chemistry Enzyme Induction Molsidomine biology.protein Macrophages Peritoneal Amino Acid Oxidoreductases Nitric Oxide Synthase Research Article |
| Zdroj: | Europe PubMed Central |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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