|
|
 Previous Article | Table of Contents | Next Article 
Nitric Oxide-Mediated Induction of Ferritin Synthesis in J774
Macrophages by Inflammatory Cytokines: Role of Selective Iron
Regulatory Protein-2 Downregulation
Stefania Recalcati,
Donatella Taramelli,
Dario Conte, and
Gaetano Cairo
From Cattedra di Gastroenterologia I, Istituto di Scienze Mediche,
IRCCS Ospedale Maggiore, Istituto di Microbiologia Medica,
Università degli Studi di Milano, and Centro di Studio sulla
Patologia Cellulare CNR, Milano, Italy.
Cytokine-treated macrophages represent a useful model to unravel the
molecular basis of reticuloendothelial (RE) iron retention in
inflammatory conditions. In the present study, we showed that stimulation of murine macrophage J774 cells with interferon
(IFN)- /lipopolysaccharide (LPS) resulted in a nitric
oxide-dependent modulation of the activity of iron regulatory proteins
(IRP)-1 and 2, cytoplasmic proteins which, binding to RNA motifs called
iron responsive elements (IRE), control ferritin translation.
Stimulation with cytokines caused a small increase of IRP-1 activity
and a strong reduction of IRP-2 activity accompanied by increased
ferritin synthesis and accumulation. Cytokines induced only a minor
increase of H chain ferritin mRNA, thus indicating that IRP-2-mediated
posttranscriptional regulation plays a major role in the control of
ferritin expression. This was confirmed by direct demonstration that
the translational repression function of IRP was impaired in stimulated
cells. In fact, translation in cell-free extracts of a reporter
transcript under the control of an IRE sequence was repressed less
efficiently by IRP-containing lysates from cytokine-treated cells than
by lysates from control cells. Our findings throw light on the role of
IRP-2 showing that: (1) this protein responds to a stimulus in opposite
fashion to IRP-1; (2) when abundantly expressed, as in J774 cells,
IRP-2 is sufficient to regulate intracellular iron metabolism in living cells; and (3) by allowing increased ferritin synthesis, IRP-2 may play
a role in the regulation of iron homeostasis in RE cells during
inflammation.
Blood, Vol. 91 No. 3 (February 1), 1998:
pp. 1059-1066
© 1998 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. Tacchini, E. Gammella, C. De Ponti, S. Recalcati, and G. Cairo
Role of HIF-1 and NF-{kappa}B Transcription Factors in the Modulation of Transferrin Receptor by Inflammatory and Anti-inflammatory Signals
J. Biol. Chem.,
July 25, 2008;
283(30):
20674 - 20686.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Niles, M. S. Clegg, L. A. Hanna, S. S. Chou, T. Y. Momma, H. Hong, and C. L. Keen
Zinc Deficiency-induced Iron Accumulation, a Consequence of Alterations in Iron Regulatory Protein-binding Activity, Iron Transporters, and Iron Storage Proteins
J. Biol. Chem.,
February 22, 2008;
283(8):
5168 - 5177.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Rejdak, A. Petzold, Z. Stelmasiak, and G. Giovannoni
Cerebrospinal fluid brain specific proteins in relation to nitric oxide metabolites during relapse of multiple sclerosis
Multiple Sclerosis,
January 1, 2008;
14(1):
59 - 66.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. Donovan, C. N. Roy, and N. C. Andrews
The Ins and Outs of Iron Homeostasis
Physiology,
April 1, 2006;
21(2):
115 - 123.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. T. Chen, L. Li, D.-H. Chung, C. D.C. Allen, S. V. Torti, F. M. Torti, J. G. Cyster, C.-Y. Chen, F. M. Brodsky, E. C. Niemi, et al.
TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis
J. Exp. Med.,
October 3, 2005;
202(7):
955 - 965.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Alberghini, S. Recalcati, L. Tacchini, P. Santambrogio, A. Campanella, and G. Cairo
Loss of the von Hippel Lindau Tumor Suppressor Disrupts Iron Homeostasis in Renal Carcinoma Cells
J. Biol. Chem.,
August 26, 2005;
280(34):
30120 - 30128.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Wang, G. Chen, and K. Pantopoulos
Nitric Oxide Inhibits the Degradation of IRP2
Mol. Cell. Biol.,
February 15, 2005;
25(4):
1347 - 1353.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Corna, P. Santambrogio, G. Minotti, and G. Cairo
Doxorubicin Paradoxically Protects Cardiomyocytes against Iron-mediated Toxicity: ROLE OF REACTIVE OXYGEN SPECIES AND FERRITIN
J. Biol. Chem.,
April 2, 2004;
279(14):
13738 - 13745.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. D. Schneider and E. A. Leibold
Effects of iron regulatory protein regulation on iron homeostasis during hypoxia
Blood,
November 1, 2003;
102(9):
3404 - 3411.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R.L. Upton, Y. Chen, S. Mumby, J.M.C. Gutteridge, P.B. Anning, A.G. Nicholson, T.W. Evans, and G.J. Quinlan
Variable tissue expression of transferrin receptors: relevance to acute respiratory distress syndrome
Eur. Respir. J.,
August 1, 2003;
22(2):
335 - 341.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Grosser and H. Schroder
Aspirin Protects Endothelial Cells From Oxidant Damage Via the Nitric Oxide-cGMP Pathway
Arterioscler. Thromb. Vasc. Biol.,
August 1, 2003;
23(8):
1345 - 1351.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Bouton, M.-J. Chauveau, S. Lazereg, and J.-C. Drapier
Recycling of RNA Binding Iron Regulatory Protein 1 into an Aconitase after Nitric Oxide Removal Depends on Mitochondrial ATP
J. Biol. Chem.,
August 16, 2002;
277(34):
31220 - 31227.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. T Gewaltig and G. Kojda
Vasoprotection by nitric oxide: mechanisms and therapeutic potential
Cardiovasc Res,
August 1, 2002;
55(2):
250 - 260.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. L. Wardrop, C. Wells, T. Ravasi, D. A. Hume, and D. R. Richardson
Induction of Nramp2 in activated mouse macrophages is dissociated from regulation of the Nramp1, classical inflammatory genes, and genes involved in iron metabolism
J. Leukoc. Biol.,
January 1, 2002;
71(1):
99 - 106.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kim and P. Ponka
Effects of Interferon-gamma and Lipopolysaccharide on Macrophage Iron Metabolism Are Mediated by Nitric Oxide-induced Degradation of Iron Regulatory Protein 2
J. Biol. Chem.,
February 25, 2000;
275(9):
6220 - 6226.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Mulero and J. H. Brock
Regulation of Iron Metabolism in Murine J774 Macrophages: Role of Nitric Oxide-Dependent and -Independent Pathways Following Activation With Gamma Interferon and Lipopolysaccharide
Blood,
October 1, 1999;
94(7):
2383 - 2389.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Tacchini, L. Bianchi, A. Bernelli-Zazzera, and G. Cairo
Transferrin Receptor Induction by Hypoxia. HIF-1-MEDIATED TRANSCRIPTIONAL ACTIVATION AND CELL-SPECIFIC POST-TRANSCRIPTIONAL REGULATION
J. Biol. Chem.,
August 20, 1999;
274(34):
24142 - 24146.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Oliveira, C. Bouton, and J.-C. Drapier
Thioredoxin Activation of Iron Regulatory Proteins. REDOX REGULATION OF RNA BINDING AFTER EXPOSURE TO NITRIC OXIDE
J. Biol. Chem.,
January 1, 1999;
274(1):
516 - 521.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. M. Brown, S. A. Anderson, D. W. Steffen, T. B. Carpenter, M. C. Kennedy, W. E. Walden, and R. S. Eisenstein
Novel role of phosphorylation in Fe-S cluster stability revealed by phosphomimetic mutations at Ser-138 of iron regulatory protein 1
PNAS,
December 22, 1998;
95(26):
15235 - 15240.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
