scholarly journals Effects of nitrogen monoxide and carbon monoxide on molecular and cellular iron metabolism: mirror-image effector molecules that target iron

2003 ◽  
Vol 370 (3) ◽  
pp. 1111-1111
Author(s):  
R.N. WATTS ◽  
P. PONKA ◽  
D.R. RICHARDSON
Keyword(s):  
Carbon Monoxide ◽  
Iron Metabolism ◽  
Nitrogen Monoxide ◽  
Mirror Image ◽  
Effector Molecules ◽  
Cellular Iron

scholarly journals Effects of nitrogen monoxide and carbon monoxide on molecular and cellular iron metabolism: mirror-image effector molecules that target iron

2003 ◽  
Vol 369 (3) ◽  
pp. 429-440 ◽  
Author(s):  
Ralph N. WATTS ◽  
Prem PONKA ◽  
Des R. RICHARDSON
Keyword(s):  
Carbon Monoxide ◽  
Nitrogen Monoxide ◽  
Preliminary Evidence ◽  
Mirror Image ◽  
Cellular Mechanisms ◽  
Iron Regulatory Proteins ◽  
Cellular Iron ◽  
Fe Complex ◽  
Oxide Synthase ◽  
Mrna Binding

Many effector functions of nitrogen monoxide (NO) and carbon monoxide (CO) are mediated through their high-affinity for iron (Fe). In this review, the roles of NO and CO are examined in terms of their effects on the molecular and cellular mechanisms involved in Fe metabolism. Both NO and CO avidly form complexes with a plethora of Fe-containing molecules. The generation of NO and CO is mediated by the nitric oxide synthase and haem oxygenase (HO) families of enzymes respectively. The effects of NO on Fe metabolism have been well characterized, whereas knowledge of the effects of CO remains within its infancy. In terms of the role of NO in Fe metabolism, one of the best characterized interactions includes its effect on the iron regulatory proteins. These molecules are mRNA-binding proteins that control the expression of the transferrin receptor 1 and ferritin, molecules that are involved in Fe uptake and storage respectively. Apart from this, activated macrophages impart their cytotoxic activity by generating NO, which results in marked Fe mobilization from tumour-cell targets. This deprives the cell of the Fe that is required for DNA synthesis and energy production. Considering that HO degrades haem, resulting in the release of CO, Fe(II) and biliverdin, it is suggested that a CO—Fe complex will form. This may account for the rapid Fe mobilization observed from macrophages after haemoglobin catabolism. Intriguingly, overexpression of HO results in cellular Fe mobilization, suggesting that CO has a similar effect to NO on Fe trafficking. Preliminary evidence suggests that, like NO, CO plays important roles in Fe metabolism.

scholarly journals Effect of nitric oxide on expression of transferrin receptor and ferritin and on cellular iron metabolism in K562 human erythroleukemia cells

Blood ◽  
1995 ◽  
Vol 85 (10) ◽  
pp. 2962-2966 ◽  
Author(s):  
R Oria ◽  
L Sanchez ◽  
T Houston ◽  
MW Hentze ◽  
FY Liew ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Iron Metabolism ◽  
Transferrin Receptor ◽  
Regulatory Protein ◽  
Inhibitory Effect ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Intracellular Iron ◽  
Cellular Iron ◽  
Erythroleukemia Cells

Nitric oxide (NO) is known to increase the affinity of the intracellular iron-regulatory protein (IRP) for iron-response elements (IREs) in transferrin receptor and ferritin mRNAs, suggesting that it may act as a regulator of cellular iron metabolism. In this study, exogenous NO produced by adding the NO-generator S-nitroso-N-acetyl penicillamine gave a dose-dependent upregulation of transferrin receptor expression by K562 erythroleukemia cells and increased levels of transferrin receptor mRNA. NO did not affect the affinity of transferrin binding by the transferrin receptor. NO alone did not alter intracellular ferritin levels, but it did abrogate the inhibitory effect of the iron chelator desferrioxamine and potentiated the stimulatory effect of additional iron. NO also caused some increase in ferritin mRNA levels, which might mask any IRP-/IRE-mediated inhibitory effect of NO on ferritin translation. Although NO did not affect net iron uptake, it increased release of iron from K562 cells pulsed previously with 59Fe, and subcellular fractionation showed that it also increased the proportion of intracellular iron bound to ferritin. These findings provide direct evidence that NO can affect cellular iron metabolism and suggest that NO produced in vivo by activated bone marrow macrophages might affect erythropoiesis.

scholarly journals Glia maturation factor-γ regulates murine macrophage iron metabolism and M2 polarization through mitochondrial ROS

2019 ◽  
Vol 3 (8) ◽  
pp. 1211-1225 ◽  
Author(s):  
Wulin Aerbajinai ◽  
Manik C. Ghosh ◽  
Jie Liu ◽  
Chutima Kumkhaek ◽  
Jianqing Zhu ◽  
...  
Keyword(s):  
Iron Metabolism ◽  
Mitochondrial Function ◽  
Regulatory Protein ◽  
M2 Macrophage ◽  
Macrophage Phenotype ◽  
Glia Maturation Factor ◽  
Altered Expression ◽  
Murine Macrophages ◽  
Cellular Iron ◽  
Maturation Factor

Abstract In macrophages, cellular iron metabolism status is tightly integrated with macrophage phenotype and associated with mitochondrial function. However, how molecular events regulate mitochondrial activity to integrate regulation of iron metabolism and macrophage phenotype remains unclear. Here, we explored the important role of the actin-regulatory protein glia maturation factor-γ (GMFG) in the regulation of cellular iron metabolism and macrophage phenotype. We found that GMFG was downregulated in murine macrophages by exposure to iron and hydrogen peroxide. GMFG knockdown altered the expression of iron metabolism proteins and increased iron levels in murine macrophages and concomitantly promoted their polarization toward an anti-inflammatory M2 phenotype. GMFG-knockdown macrophages exhibited moderately increased levels of mitochondrial reactive oxygen species (mtROS), which were accompanied by decreased expression of some mitochondrial respiration chain components, including the iron-sulfur cluster assembly scaffold protein ISCU as well as the antioxidant enzymes SOD1 and SOD2. Importantly, treatment of GMFG-knockdown macrophages with the antioxidant N-acetylcysteine reversed the altered expression of iron metabolism proteins and significantly inhibited the enhanced gene expression of M2 macrophage markers, suggesting that mtROS is mechanistically linked to cellular iron metabolism and macrophage phenotype. Finally, GMFG interacted with the mitochondrial membrane ATPase ATAD3A, suggesting that GMFG knockdown–induced mtROS production might be attributed to alteration of mitochondrial function in macrophages. Our findings suggest that GMFG is an important regulator in cellular iron metabolism and macrophage phenotype and could be a novel therapeutic target for modulating macrophage function in immune and metabolic disorders.

The role of reactive oxygen and nitrogen species in cellular iron metabolism

2006 ◽  
Vol 40 (3) ◽  
pp. 263-272 ◽  
Author(s):  
PŘEMYSL MLADĚNKA ◽  
TOMÁŠ ŠIMŮNEK ◽  
MOJMÍR HÜBL ◽  
RADOMÍR HRDINA
Keyword(s):  
Iron Metabolism ◽  
Reactive Oxygen ◽  
Nitrogen Species ◽  
Cellular Iron

scholarly journals Human Mitochondrial Ferritin Expressed in HeLa Cells Incorporates Iron and Affects Cellular Iron Metabolism

2002 ◽  
Vol 277 (25) ◽  
pp. 22430-22437 ◽  
Author(s):  
Barbara Corsi ◽  
Anna Cozzi ◽  
Paolo Arosio ◽  
Jim Drysdale ◽  
Paolo Santambrogio ◽  
...  
Keyword(s):  
Iron Metabolism ◽  
Hela Cells ◽  
Cellular Iron

Abstract 4365: Induction of distinct p53 mutation types differentially influences the control of cellular iron metabolism

2019 ◽  
Author(s):  
Eshan Dandekar ◽  
Aishwarya Srinivasan ◽  
Stephen Clarke ◽  
Mckale Montgomery
Keyword(s):  
Iron Metabolism ◽  
P53 Mutation ◽  
Cellular Iron
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